ToxSci Advance Access originally published online on June 1, 2006
Toxicological Sciences 2006 93(1):96-104; doi:10.1093/toxsci/kfl026
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Mechanisms of Particle-Induced Pulmonary Inflammation in a Mouse Model: Exposure to Wood Dust
* Department of Industrial Hygiene and Toxicology, Department of Occupational Medicine, and Lappeenranta Regional Institute of Occupational Health, Lappeenranta, Finland 53850; Finnish Institute of Occupational Health, Helsinki, Finland 00250
1 To whom correspondence should be addressed at Unit of Excellence in Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland. Fax: +358-30-4742116. E-mail: harri.alenius{at}ttl.fi.
Received December 22, 2005; accepted May 23, 2006
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Repeated airway exposure to wood dust has long been known to cause adverse respiratory effects such as asthma and chronic bronchitis and impairment of lung function. However, the mechanisms underlying the inflammatory responses of the airways after wood dust exposure are poorly known. We used a mouse model to elucidate the mechanisms of particle-induced inflammatory responses to fine wood dust particles. BALB/c mice were exposed to intranasally administered fine (more than 99% of the particles had a particle size of
5 µm, with virtually identical size distribution) birch or oak dusts twice a week for 3 weeks. PBS, LPS, and titanium dioxide were used as controls. Intranasal instillation of birch or oak dusts elicited influx of inflammatory cells to the lungs in mice. Enhancement of lymphocytes and neutrophils was seen after oak dust exposure, whereas eosinophil infiltration was higher after birch dust exposure. Infiltration of inflammatory cells was associated with an increase in the mRNA levels of several cytokines, chemokines, and chemokine receptors in lung tissue. Oak dust appeared to be a more potent inducer of these inflammatory mediators than birch dust. The results from our in vivo mouse model show that repeated airway exposure to wood dust can elicit lung inflammation, which is accompanied by induction of several proinflammatory cytokines and chemokines. Oak and birch dusts exhibited quantitative and qualitative differences in the elicitation of pulmonary inflammation, suggesting that the inflammatory responses induced by the wood species may rise via different cellular mechanisms. Key Words: chemokines; cytokines; gene expression; leukocytes.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Wood dust, generated in the processing of wood, can induce several diseases of the respiratory track. Reported nonmalignant diseases and symptoms associated with wood dust exposure include allergic rhinitis, chronic bronchitis, asthma, allergic alveolitis, and organic dust toxic syndrome (Bohadana et al., 2000
; De Zotti and Gubian, 1996; Douwes et al., 2001; Enarson and Chan-Yeung, 1990; Goldsmith and Shy, 1988). Evidence from epidemiological studies reveals that most wood species can induce occupational asthma (SCOEL, 2003). However, in some cases, the symptoms can be attributable, at least in part, to bacteria and fungi that can be abundant in wood dust especially in warm, humid conditions (Weber et al., 1993).
Increase in blood eosinophilia as well as elevated prevalence of positive methacholine bronchial challenge have been reported in workers handling hard- and softwoods (Bohadana et al., 2000; De Zotti and Gubian, 1996; Gripenback et al., 2005). Wintermeyer et al. (1997) detected an increase in IL-8 level in bronchoalveolar lavage (BAL) fluid and an elevation in neutrophil percentage after exposure of healthy volunteers to wood chip mulch dust. Also increased numbers of T lymphocytes and eosinophils in BAL fluid have been reported in the airways when healthy people were exposed to pine dust (Gripenback et al., 2005). Plicatic acid has been identified to be the causative agent of western red cedar asthma (Chan-Yeung, 1994). However, western red cedar asthma and the release of histamine induced by plicatic acid do not appear to be dependent on plicatic acid–specific immunoglobulin E (IgE) antibodies in most individuals (Frew et al., 1993). Therefore, unidentified cell-dependent immunologic mechanisms have been suggested. Despite a few reports in the literature, our knowledge of cellular mechanisms underlying wood dust–induced airway symptoms is surprisingly poor.
Our recent findings demonstrate that exposure to wood dust can modulate the expression of macrophage-derived cytokines and chemokines (Maatta et al., 2005). Birch and oak dust exposure induced several proinflammatory cytokines and chemokines in mouse macrophage RAW 264.7 cell line cells. In the present study, we utilized a murine model to examine cellular mechanisms by which exposure to fine wood dust particles induces inflammatory responses in the airways.
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MATERIALS AND METHODS |
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Study design.
Due to the sparse literature data available on the nature and molecular mechanisms of the airway inflammation associated with occupational wood dust exposure, we decided to investigate expression of a relatively wide range of cytokines, chemokines, and chemokine receptors. The overall aim of the study was to narrow down molecular events behind the inflammatory response in order to generate more accurate hypotheses. To have an approach feasible to carry out in practice and, simultaneously, sensitive enough to elucidate crucial changes in the expression levels, we examined gene expression as mRNA induction in the murine lungs. In our murine in vivo model, we investigated expression of major proinflammatory (TNF-
, IL-1ß), Th2 (IL-4, IL-5, IL-13), Th1 (IFN-
, IL-12 p40), and regulatory (TGF-ß1) cytokines using real-time PCR. These cytokine groups give information about the immunological status of the airways regarding, for example, development of allergic response (Th2 cytokines) or imbalance of the regulatory system. To investigate further the mechanisms of pulmonary inflammation, we measured several chemokines (CCL2–4, CCL8, CCL11–12, CCL17, CCL20, CXCL2/3, CXCL5) and chemokine receptors (CCR1–5, CCR8, CXCR2) which critically regulate recruitment of distinct leukocyte subsets to the site of the inflammation (Murphy et al., 2000; Onuffer and Horuk, 2002; Zlotnik and Yoshie, 2000). In addition, airway responses to inhaled methacholine were investigated in order to have functional information about the development of bronchial hyperreactivity. Finally, we measured antibody responses for receiving essential information about B-cell–mediated immune reactions (IgE was studied as a surrogate marker for Th2 and IgG2a as a surrogate marker for Th1). Prior to these investigations, pulmonary inflammation was analyzed using histological techniques and differential cell counts in BAL samples.
Animals.
Six- to 8-week-old female BALB/c mice were purchased from Taconic M&B A/S (Ry, Denmark). All experiments were approved by the Social and Health Services of the Provincial Office of Southern Finland.
Wood dusts, TiO2, and LPS.
Carefully prepared wood dusts from oak (Quercus alba) and birch (Betula pendula) were used in the experiments. Physicochemical characteristics of both wood materials are given in Table 1. The starting material for oak and birch dusts were industrially dried, knotless birch and oak board obtained from a carpenter company (Puusepänliike Pöntinen KY, Lappeenranta, Finland). Wood dusts were generated using a band saw. The exhaust air of the saw was led into a vertical elutriator (diameter 1 m, height 3.5 m), where slow upward airflow separated the fine dust from chips and coarse particles. The coarse dust fell down and the fine dust was ducted from the upper part of the vertical elutriator. The size distribution of wood dust particles was monitored in real time with a laser particle monitor (Hiac/Royco 5000, Pacific Scientific, Silver Spring, MD) in the output duct of the vertical elutriator. More than 99% of birch and oak dust particles had a particle size 5 µm (Fig. 1). After particle size monitoring, the wood dust was collected on membrane filters at the end of the output duct. The endotoxin concentrations were 400 pg/mg for birch dust and 140 pg/mg for oak dust (Limulus Amebocyte Lysate test). Titanium dioxide (TiO2) powder (Aldrich Chemical Co, Milwaukee, WI), predominantly rutile, had a particle size less than 5 µm (scanning electron microscopy). LPS from Shigella flexneri serotype 1A (Sigma, St Louis, MO) was dissolved in PBS and sterile filtered before use.
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Study protocol, measurement of airway hyperreactivity, and collection of samples.
Intranasal instillation was selected as the route of exposure since it is widely used, easy to standardize, and simple to perform. The wood dusts, TiO2, LPS, or PBS suspensions were administered intranasally under light anesthesia using isoflurane (Abbott Laboratories Ltd, Queenborough, England) two times a week for 3 weeks. Mice received either 0.5 or 50 µg wood dust or TiO2 in 50 µl of PBS in the nostrils. Control mice were given 50 µl PBS or LPS at the same concentration as LPS in birch dust (20 pg/50 µl). On day 19, the airway hyperreactivity to methacholine (Sigma-Aldrich Co, St Louis, MO) was measured using whole-body plethysmography (Buxco Electronics, Inc., Sharon, CT) as previously described (Hamelmann et al., 1997
). The enhanced pause (PenH) values were averaged and expressed as the percentage of baseline PenH values (% baseline PenH). The mice were then sacrificed with CO2 and samples (blood, BAL fluids, and lung biopsies) collected. BAL samples were prepared by lavaging lungs once with 0.8 ml of PBS via trachea, cytocentrifugated (Shandon Scientific Ltd, Runcorn, UK), and stained with May-Grünwald-Giemsa. Cells were counted in 40 high-power fields at x1000 under light microscopy (Nikon EclipseE800, Leica Microsystems GmbH, Wetzlar, Germany). The left lung was removed for RNA isolation, quick-frozen, and kept at – 70°C. For histological examination, the right lung was perfused with 10% formalin (500 µl) and stored in formalin for 24 h. Formalin-fixed lungs were embedded in paraffin and cut into 5-µm-thick sections. The slides were stained with hematoxylin and eosin, and the amount of lung inflammation was examined under light microscopy.
RNA isolation, reverse transcription, and real-time quantitative PCR.
RNA isolation, cDNA synthesis, and real-time–quantitative PCR were performed as earlier described (Lehto et al., 2003). The primers and probes used were obtained from Applied Biosystems (Foster City, CA) as predeveloped reagents or were self-designed (Maatta et al., 2005). The primer and probe sequences for self-designed CCR3 and CCR4 were as follows: CCR3 forward primer 5'-TTG CAG GAC TGG CAG CAT T-3', CCR3 reverse primer 5'-TTC ATT CTT AGA GCA TGG AAA CGT T-3', CCR3 probe 5'-TGG AGA GTT TTC CTG CAG TCC TCG CTA TC-3', CCR4 forward primer 5'-TCA TGA CTT CCG TGA CGC TTT-3', CCR4 reverse primer 5'-GTT TTC TTC CTC AGA GCC CTG TT-3', and CCR4 probe 5'-TCG CCT TGT TTC AGT CAG GGT GCC-3'. The relative quantity was calculated by the comparative CT method according to the manufacturer's instructions.
Measurement of serum antibodies.
Serum levels of total IgE were measured by ELISA as previously described (Lehto et al., 2003). The same ELISA protocol was used for total IgG2a measurement. Briefly, at first the plates were coated with rat anti-mouse IgG2a monoclonal antibodies (clone R11-89). After blocking, samples were added and bound IgG2a was detected with biotin-conjugated rat anti-mouse IgG2a (clone R19-15). Streptavidin horseradish peroxidase followed by substrate was used to detect the bound antibody levels, and the optical density was measured at 405 nm. Total IgG2a levels were calculated by comparing with mouse IgG2a (clone G155-178). The standard and antibodies for ELISA were purchased from BD Biosciences (San Diego, CA).
Statistical analysis.
The data were analyzed with the GraphPadPrism Software version 4.00 (GraphPad Software, Inc., San Diego, CA). Single-group comparisons were performed by the Mann-Whitney test. The results are expressed as mean ± SEM. p values < 0.05 were considered to be statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Wood Dust Instillation Induces Inflammatory Cell Infiltration to the Lungs
Histological examination revealed modest but clear-cut changes in the lung morphology after the wood dust exposure (Fig. 2A). Eosinophil infiltration was dominating in mice exposed to higher concentration of birch dust (50 µg/50 µl), whereas exposure to higher concentration of oak dust caused an influx of neutrophils and lymphocytes into the lungs (Fig. 2A inserts). No detectable histological signs of lung inflammation were found after LPS control or TiO2 (Fig. 2A) exposure or after exposure to lower wood dust concentration (0.5 µg/50 µl) (data not shown).
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A clear influx of inflammatory cells into the BAL was observed after instillations of higher concentration of birch and oak dusts (Fig. 2B). In line with the histological findings, lymphocyte infiltration in BAL was significantly higher in mice exposed to oak dust than in those exposed to birch dust. Similarly, oak dust exposure also induced higher infiltration of neutrophils than birch dust, although the difference did not reach statistical significance (Fig. 2B). On the other hand, birch dust caused a significantly higher influx of eosinophils into the BAL than oak dust. TiO2 dust induced a statistically significant, but weak, increase in the amount of neutrophils than PBS-treated mice (Fig. 2B).
Microscopic analyses revealed that all particles tested (oak, birch, TiO2) were readily internalized by alveolar macrophages (Fig. 3). There were no significant differences in the number of ingested particles after oak or birch dust administration (data not shown).
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Cytokine Expression Is Induced in Wood Dust–Exposed Lungs
Proinflammatory cytokines are produced by activated leukocytes to start a cascade of inflammatory reactions. As shown in Figure 4, there was a significant induction in the mRNA expression of proinflammatory cytokines IL-1ß and TNF-
in the mice lungs after repeated instillations of higher concentration of oak dust. The effect of birch dust was weaker. Birch dust induced significantly only TNF- mRNA expression compared to PBS-control group. TiO2 dust did not have any significant effect on IL-1ß or TNF- mRNA expression (Fig. 4). The mRNA expression of regulatory cytokine TGF-ß1 was induced significantly in oak dust–exposed lungs (Fig. 4).
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There was no significant increase in the mRNA expression of the major Th1 (IFN-
and IL-12 p40) or Th2 cytokines (IL-4, IL-5, and IL-13) after exposure to either wood dust (data not shown). The lower dust concentration, LPS control, or TiO2 dust did not induce any of the cytokines studied (Fig. 4, data not shown).
Chemokines and Their Receptors Are Significantly Induced in Wood Dust–Exposed Lungs
Chemokines are small cytokines that critically regulate the recruitment of leukocytes to the site of inflammation (Zlotnik and Yoshie, 2000). Expression of several chemokines was significantly induced in the lung tissue after wood dust instillations as shown in Figure 5. Compared with mice exposed to PBS only, CCL3, CCL17, and CXCL2/3 chemokines were induced significantly by both birch and oak dusts. Oak dust also induced significantly CCL2, CCL4, CCL8, CCL11, CCL12, CCL20, and CXCL5 chemokines. Compared to PBS-treated mice, TiO2 induced significantly CCL3, CCL4, and CXCL2/3 chemokines. In general, the inducing effect of TiO2 was weaker than that of wood dusts. However, induction of CCL3 mRNA was comparable to TiO2, birch, and oak dust exposures.
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The higher concentration of both birch and oak dust induced significantly the expression of CCR1, CCR2, and CCR5 chemokine receptors in the lungs (Fig. 6). Oak dust induced significantly also CCR3, CCR4, CCR8, and CXCR2 chemokine receptors (Fig. 6). TiO2, the lower wood dust concentration, or LPS did not induce significantly any of the chemokines and chemokine receptors studied.
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Bronchial Reactivity to Inhaled Methacholine and Humoral Response Were Not Affected Significantly After Wood Dust Exposure
Methacholine-induced bronchial reactivity was not altered after exposures to wood dusts, LPS, or TiO2 (Fig. 7). No significant increase in the levels of total IgE or IgG2a was found after any exposure (data not shown).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Repeated airway exposure to wood dust has long been known to cause adverse respiratory effects and impairment of lung function (Demers et al., 1997
; Enarson and Chan-Yeung, 1990; Goldsmith and Shy, 1988). However, the mechanisms underlying the inflammatory responses of the airways after wood dust exposure are poorly known.
In the present study we used a murine model to investigate effects of repeated, intranasally administered, oak and birch dust exposures on lung functions and airway inflammation. Oak and birch dust were selected since oak dust has been reported to induce several malignant and nonmalignant diseases, whereas birch dust has appeared to be less hazardous (Klein et al., 2001; Malo et al., 1995; Mohtashamipur et al., 1989; Nylander and Dement, 1993). In vivo experiments were performed using very fine birch and oak dusts (more than 99% of the particles had a particle size 5 µm). In addition, particle size distribution of birch and oak dusts was virtually identical (see Fig. 1). Therefore, a considerable number of the wood dust particles, administered intranasally to mice under light anesthesia, were expected to reach the alveolar regions of the lungs. Indeed, the macrophages in the BAL contained plenty of wood dust or TiO2 particles, depending on the exposure. Since alveolar macrophages account for up to 95% of cells in BAL in noninflammatory conditions (Gordon and Read, 2002), these observations indicate that intranasally administered very fine wood dust (or TiO2) reaches the alveolar region of the lungs.
Allergic asthma is characterized by infiltration of eosinophils and lymphocytes to the airways (Hamid et al., 2003). Exposure to pinewood dust increases numbers of eosinophils, T cells, and mast cells in the BAL fluids in healthy individuals (Gripenback et al., 2005). In the present study, we observed an increase in the number of macrophages, neutrophils, lymphocytes, and eosinophils in the tissue and BAL fluid after repeated birch or oak dust instillations. Lymphocytes and neutrophils dominated after oak dust exposures and eosinophils after birch dust exposures. Our results indicate that different wood species may induce differences in inflammatory responses although dust particle size distribution between the wood species is identical. TiO2 dust did not induce macrophages, lymphocytes, or eosinophils and induced only a weak increase in the neutrophils in the BAL fluid, suggesting that the much stronger increase in the inflammatory cells after wood dust instillations is wood dust specific.
In order to study the cytokine milieu in wood dust–exposed lungs, we analyzed the expression of major proinflammatory, Th2 and Th1 cytokines. No significant changes in the expression of Th1 or Th2 cytokines were observed with either of the wood dusts. On the contrary, repeated exposure to oak dust induced IL-1ß and TNF- mRNA expression in lung tissue, whereas birch dust exposure induced significantly only TNF- mRNA expression. IL-1ß and TNF- protein levels in the BAL were below the detection limit due to insufficient sensitivity of the ELISA (Haapakoski and Alenius, unpublished data). TNF- has been postulated to be a critical mediator contributing to the airway inflammation in asthma since neutralization of TNF- reduced the lung inflammation in a murine model of asthma induced by a house dust extract (Kim et al., 2006). Moreover, induction of IL-1ß expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates (Lappalainen et al., 2005). Our findings are consistent with several studies that show that proinflammatory cytokines play a central role in the development of lung inflammation induced by exposure to organic dust, mineral fibers, or fungal spores (Dorger and Krombach, 2002; Driscoll, 2000; Mansour and Levitz, 2002; Vanhee et al., 1995; Yucesoy et al., 2002).
Present results suggest that oak dust in particular has a major impact on the expression of proinflammatory cytokines and that this effect is not significantly affected by the interaction of resident lung cells with particles per se. Because both the tested wood dusts had a practically identical size distribution profile and because their endotoxin content was so low that similar amount of LPS in the control mice did not induce any detectable response, the most likely explanation for the differences between oak and birch dust–induced cytokine expressions seems to be the chemical composition of these wood dusts. Further studies are needed to examine the specific role of various chemical components present in the wood dusts (Table 1) in the elicitation of inflammatory reactions demonstrated in the present study.
We observed that mRNA expression of regulatory cytokine TGF-ß was increased in the mice exposed to oak dust. TGF-ß has many anti-inflammatory and regulatory functions (Borish and Steinke, 2003; Cerwenka and Swain, 1999). Because it regulates the production of many extracellular matrix components and promotes fibrosis, the wood dust–induced upregulation of TGF-ß production, observed in this study, might have some role in the development of cryptogenic fibrosing alveolitis that has been suggested to be induced by wood dust exposure (Hubbard, 2001; Hubbard et al., 1996; Scott et al., 1990; Tatrai et al., 1995). TGF-ß has also been reported to modulate extracellular matrix synthesis and fibronectin content in type II pulmonary epithelial cell cultures exposed to coal dust (Lee and Rannels, 1998). Moreover, the alveolar macrophages from patients who have either chronic bronchitis or asthma release increased amounts of TGF-ß and fibronectin—in asthma, however, to a lesser degree (Vignola et al., 1996).
To investigate further the mechanisms of leukocyte infiltration in our murine model, we studied the expression profiles of several chemokines and their receptors in the lungs. In general, oak dust appears to be a stronger inducer of a wide variety of chemokines compared to birch dust. TiO2 induced significantly only CCL3, CCL4, and CXCL2/3 chemokines. The two nonpolarized chemokines, CCL3 and CCL4, are also induced in RAW 264.7 macrophages after TiO2 dust exposure (Maatta et al., 2005), suggesting that their expression is upregulated when macrophages come into contact with any foreign particles. The upregulation of chemokine expression after wood dust exposure was accompanied by the upregulation of their specific receptors: CCR1 (the receptor of CCL3; present on various lymphocytes), CCR2 (the receptor of CCL2 and CCL12; present on various lymphocytes), CCR3 (the receptor of CCL5 and CCL11; present mainly on eosinophils and mast cells), CCR4 (the receptor of CCL17; present especially on Th2 cells), CCR5 (the receptor of CCL3 and CCL4; present especially on Th1 cells), and CXCR2 (the receptor of CXCL2/3 and CXCL5; present especially on neutrophils). These receptors are expressed on inflammatory cells (e.g., macrophages, neutrophils, Th2 and Th1, lymphocytes, and eosinophils) (Murphy et al., 2000; Onuffer and Horuk, 2002), which are also increased in the lung tissue and in BAL fluid after wood dust instillations. It is of interest that mRNA expression of CCL20, CCR4, and CCR8 was significantly higher after oak dust exposure compared to birch dust or TiO2 exposure. CCL20 has been shown to be important in the recruitment of immature dendritic cells to the airways, whereas CCR4 and CCR8 have been reported to be expressed especially on Th2 cells (Onuffer and Horuk, 2002; Zlotnik and Yoshie, 2000). Whether these mediators play an important role in the pathobiology of oak dust–induced airways symptoms should be explored in further studies.
Airway hyperresponsiveness and increased levels of Th2 cytokines in the lungs together with the production of IgE antibodies are characteristics of allergic asthma (Oettgen and Geha, 2001). However, bronchial responsiveness to inhaled methacholine was not altered significantly between different mice groups in the present study. Moreover, there was no significant increase in the expression of Th2 cytokines in the lungs, and total IgE remains at the baseline level after wood dust exposure. Present findings therefore suggest that rather than induction of Th2-dominated allergic response, wood dust exposure favors the development of pulmonary inflammation in which macrophages, neutrophils, and nonpolarized lymphocytes, as well as proinflammatory cytokines, play a central role. It is of interest, however, that exposure to birch dust also elicited recruitment of eosinophils into the airways, a phenomenon which is usually associated with allergic asthma and Th2-type inflammation. On the other hand, exposure to oak dust elicited selectively increased expression of Th2-associated chemokine receptors (CCR4 and CCR8). It should be noted, however, that in addition to expression on Th2 lymphocytes these chemokine receptors are also expressed on the surface of several other cells (Murphy et al., 2000; Onuffer and Horuk, 2002; Zlotnik and Yoshie, 2000). Further studies are needed to examine whether longer exposure time with wood dust would induce development of classical signs of allergic asthma.
Taken together, our results show that repeated airway exposure to wood dust can elicit lung inflammation, which is accompanied by induction of several proinflammatory cytokines and chemokines in mice. Oak and birch dust exposure elicited quantitative and qualitative differences in pulmonary inflammation, suggesting that different wood species may also have differences in elicitation of inflammatory responses. Further studies are needed to characterize and purify bioactive components from the wood dusts and examine their effects in the mouse model.
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ACKNOWLEDGMENTS |
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This study was supported by the EU 5th Framework Programme, Key Action 4, Environment and Health, Quality of Life and Management of Living Resources (Project No. QLK4-2000-00573) and The Finnish Work Environment Fund (Project No. 104097). We gratefully acknowledge the technical expertise and assistance of Heidi Haataja, Pentti Närhi, Antti Muurikka, and Timo Tuomi from the Finnish Institute of Occupational Health.
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REFERENCES |
|---|
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Bohadana, A. B., Massin, N., Wild, P., Toamain, J. P., Engel, S., and Goutet, P. (2000). Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers. Occup. Environ. Med. 57, 268–273.
Borish, L. C., and Steinke, J. W. (2003). 2. Cytokines and chemokines. J. Allergy Clin. Immunol. 111, S460–S475.[CrossRef][Medline]
Cerwenka, A., and Swain, S. L. (1999). TGF-beta1: Immunosuppressant and viability factor for T lymphocytes. Microbes Infect. 1, 1291–1296.[CrossRef][ISI][Medline]
Chan-Yeung, M. (1994). Mechanism of occupational asthma due to western red cedar (Thuja plicata). Am. J. Ind. Med. 25, 13–18.[ISI][Medline]
De Zotti, R., and Gubian, F. (1996). Asthma and rhinitis in wooding workers. Allergy Asthma Proc. 17, 199–203.[ISI][Medline]
Demers, P. A., Teschke, K., and Kennedy, S. M. (1997). What to do about softwood? A review of respiratory effects and recommendations regarding exposure limits. Am. J. Ind. Med. 31, 385–398.[CrossRef][ISI][Medline]
Dorger, M., and Krombach, F. (2002). Response of alveolar macrophages to inhaled particulates. Eur. Surg. Res. 34, 47–52.[CrossRef][ISI][Medline]
Douwes, J., McLean, D., Slater, T., and Pearce, N. (2001). Asthma and other respiratory symptoms in New Zealand pine processing sawmill workers. Am. J. Ind. Med. 39, 608–615.[CrossRef][ISI][Medline]
Driscoll, K. E. (2000). TNFalpha and MIP-2: Role in particle-induced inflammation and regulation by oxidative stress. Toxicol. Lett. 112–113, 177–183.
Enarson, D. A., and Chan-Yeung, M. (1990). Characterization of health effects of wood dust exposures. Am. J. Ind. Med. 17, 33–38.[ISI][Medline]
Frew, A., Chan, H., Dryden, P., Salari, H., Lam, S., and Chan-Yeung, M. (1993). Immunologic studies of the mechanisms of occupational asthma caused by western red cedar. J. Allergy Clin. Immunol. 92, 466–478.[CrossRef][ISI][Medline]
Goldsmith, D. F., and Shy, C. M. (1988). Respiratory health effects from occupational exposure to wood dusts. Scand. J. Work Environ. Health 14, 1–15.[ISI][Medline]
Gordon, S. B., and Read, R. C. (2002). Macrophage defences against respiratory tract infections. Br. Med. Bull. 61, 45–61.
Gripenback, S., Lundgren, L., Eklund, A., Liden, C., Skare, L., Tornling, G., and Grunewald, J. (2005). Accumulation of eosinophils and T-lymphocytes in the lungs after exposure to pinewood dust. Eur. Respir. J. 25, 118–124.
Hamelmann, E., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G. L., Irvin, C. G., and Gelfand, E. W. (1997). Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am. J. Respir. Crit. Care Med. 156, 766–775.
Hamid, Q., Tulic, M. K., Liu, M. C., and Moqbel, R. (2003). Inflammatory cells in asthma: Mechanisms and implications for therapy. J. Allergy Clin. Immunol. 111, S5–S12; discussion S12–S17.
Hausen, B. M. (1981). Woods Injurious to Human Health. De Guyter, New York.
Hubbard, R. (2001). Occupational dust exposure and the aetiology of cryptogenic fibrosing alveolitis. Eur. Respir. J. Suppl. 32, 119s–121s.[Medline]
Hubbard, R., Lewis, S., Richards, K., Johnston, I., and Britton, J. (1996). Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis. Lancet 347, 284–289.[CrossRef][ISI][Medline]
Kim, J., McKinley, L., Natarajan, S., Bolgos, G. L., Siddiqui, J., Copeland, S., and Remick, D. G. (2006). Anti-tumor necrosis factor-alpha antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust. Clin. Exp. Allergy 36, 122–132.[CrossRef][ISI][Medline]
Klein, R. G., Schmezer, P., Amelung, F., Schroeder, H. G., Woeste, W., and Wolf, J. (2001). Carcinogenicity assays of wood dust and wood additives in rats exposed by long-term inhalation. Int. Arch. Occup. Environ. Health 74, 109–118.[CrossRef][ISI][Medline]
Lappalainen, U., Whitsett, J. A., Wert, S. E., Tichelaar, J. W., and Bry, K. (2005). Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am. J. Respir. Cell Mol. Biol. 32, 311–318.
Lee, Y. C., and Rannels, D. E. (1998). Regulation of extracellular matrix synthesis by TNF-alpha and TGF-beta1 in type II cells exposed to coal dust. Am. J. Physiol. 275, L637–L644.
Lehto, M., Koivuluhta, M., Wang, G., Amghaiab, I., Majuri, M. L., Savolainen, K., Turjanmaa, K., Wolff, H., Reunala, T., Lauerma, A., et al. (2003). Epicutaneous natural rubber latex sensitization induces T helper 2-type dermatitis and strong prohevein-specific IgE response. J. Invest. Dermatol. 120, 633–640.[CrossRef][ISI][Medline]
Maatta, J., Majuri, M. L., Luukkonen, R., Lauerma, A., Husgafvel-Pursiainen, K., Alenius, H., and Savolainen, K. (2005). Characterization of oak and birch dust-induced expression of cytokines and chemokines in mouse macrophage RAW 264.7 cells. Toxicology 215, 25–36.[CrossRef][ISI][Medline]
Malo, J. L., Cartier, A., Desjardins, A., Van de Weyer, R., and Vandenplas, O. (1995). Occupational asthma caused by oak wood dust. Chest 108, 856–858.
Mämmelä, P. (2001). Phenolics in selected European hardwood species by liquid chromatography-electrospray ionisation mass spectrometry. Analyst 126, 1535–1538.
Mämmelä, P., Savolainen, H., Lindroos, L., Kangas, J., and Vartiainen, K. (2000). Analysis of oak tannins by liquid chromatography-electrospray ionisation mass spectrometry. J. Chromatogr. A 891, 75–83.
Mansour, M. K., and Levitz, S. M. (2002). Interactions of fungi with phagocytes. Curr. Opin. Microbiol. 5, 359–365.[CrossRef][ISI][Medline]
Mohtashamipur, E., Norpoth, K., and Luhmann, F. (1989). Cancer epidemiology of woodworking. J. Cancer Res. Clin. Oncol. 115, 503–515.[CrossRef][ISI][Medline]
Murphy, P. M., Baggiolini, M., Charo, I. F., Hebert, C. A., Horuk, R., Matsushima, K., Miller, L. H., Oppenheim, J. J., and Power, C. A. (2000). International Union of Pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol. Rev. 52, 145–176.
Nylander, L. A., and Dement, J. M. (1993). Carcinogenic effects of wood dust: Review and discussion. Am. J. Ind. Med. 24, 619–647.[ISI][Medline]
Oettgen, H. C., and Geha, R. S. (2001). IgE regulation and roles in asthma pathogenesis. J. Allergy Clin. Immunol. 107, 429–440.[CrossRef][ISI][Medline]
Onuffer, J. J., and Horuk, R. (2002). Chemokines, chemokine receptors and small-molecule antagonists: Recent developments. Trends Pharmacol. Sci. 23, 459–467.[CrossRef][Medline]
Scientific Committee for Occupational Exposure Limits, SCOEL. (2003). Recommendations of the Scientific Committee for Occupational Exposure Limits: Risk Assessment for Wood Dust. European Commission, Employment and Social Affairs DG, Luxembourg.
Scott, J., Johnston, I., and Britton, J. (1990). What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust. Br. Med. J. 301, 1015–1017.[ISI][Medline]
Tatrai, E., Adamis, Z., Bohm, U., Meretey, K., and Ungvary, G. (1995). Role of cellulose in wood dust-induced fibrosing alveo-bronchiolitis in rat. J. Appl. Toxicol. 15, 45–48.[ISI][Medline]
Vanhee, D., Gosset, P., Boitelle, A., Wallaert, B., and Tonnel, A. B. (1995). Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. Eur. Respir. J. 8, 834–842.[Abstract]
Vignola, A. M., Chanez, P., Chiappara, G., Merendino, A., Zinnanti, E., Bousquet, J., Bellia, V., and Bonsignore, G. (1996). Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases. Clin. Exp. Immunol. 106, 114–119.[CrossRef][ISI][Medline]
Weber, S., Kullman, G., Petsonk, E., Jones, W. G., Olenchock, S., Sorenson, W., Parker, J., Marcelo-Baciu, R., Frazer, D., and Castranova, V. (1993). Organic dust exposures from compost handling: Case presentation and respiratory exposure assessment. Am. J. Ind. Med. 24, 365–374.[ISI][Medline]
Wintermeyer, S. F., Kuschner, W. G., Wong, H., D'Alessandro, A., and Blanc, P. D. (1997). Pulmonary responses after wood chip mulch exposure. J. Occup. Environ. Med. 39, 308–314.[CrossRef][ISI][Medline]
Yucesoy, B., Vallyathan, V., Landsittel, D. P., Simeonova, P., and Luster, M. I. (2002). Cytokine polymorphisms in silicosis and other pneumoconioses. Mol. Cell. Biochem. 234–235, 219–224.[CrossRef]
Zlotnik, A., and Yoshie, O. (2000). Chemokines: A new classification system and their role in immunity. Immunity 12, 121–127.[CrossRef][ISI][Medline]
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