ToxSci Advance Access published online on September 26, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg239
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 Department of Environmental Health, Boston University Schools of Medicine and Public Health, Boston, MA; Department of Microbiology, Boston University Schools of Medicine and Public Health, Boston, MA
* To whom correspondence should be addressed. E-mail: dsherr{at}bu.edu.
Environmental polycyclic aromatic hydrocarbons and related halogenated hydrocarbons are immunotoxic in a variety of systems. In a model system of B lymphopoiesis, PAH exposure rapidly induces apoptosis in CD43- pre-B and CD43+ pro/pre-B cells. Apoptosis induction by 7,12-dimethylbenzo[a]anthracene (DMBA) is dependent upon AhR+ bone marrow stromal cells and likely involves DMBA metabolism within the stromal cell. However, it is not known if PAH-treated stromal cells release free metabolites or soluble factors that may directly induce B cell death or if the effector death signal is delivered by stromal cell-B cell contact. Here, we demonstrate that supernatants from DMBA-treated bone marrow stromal cells contain an activity capable of inducing apoptosis in pro/pre-B cells co-cultured with stromal cells. This activity: 1) is not produced when stromal cells are co-treated with DMBA and
© 2003 Society of Toxicology
Immunotoxicology
Bone Marrow Stromal-B Cell Interactions in Polycyclic Aromatic Hydrocarbon-Induced Pro/Pre-B Cell Apoptosis
2 Lady Davis Institute for Medical Research, Montreal, Canada
3 The Burdock Group, Vero Beach, FlA
4 Department of Environmental Health, Boston University Schools of Medicine and Public Health, Boston, MA
Abstract 
-naphthoflavone, an AhR and cytochrome P-450 inhibitor, 2) is 
50 kDa, 3) is trypsin and heat sensitive, and 4) is dependent on AhR+ stromal cells which in turn deliver the effector death signal to pro/pre-B cells. The results: 1) argue against a role for a soluble, stromal cell-derived cytokine as the effector of PAH-induced pro/pre-B cell death, 2) exclude the possibility of a free metabolite acting directly on AhR- pro/pre-B cell targets, and 3) suggest the elaboration by stromal cells of a relatively stable, DMBA metabolite-protein complex capable of acting on other stromal cells at some distance. Collectively, these studies suggest that while stromal cell products, e.g. metabolite-protein complexes, may affect the function of distant stromal cells, the effector death signal delivered by stromal cells to bone marrow B cells is mediated by cell-cell contact.
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