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Toxicological Sciences 59, 108-117 (2001)
Copyright © 2001 by the Society of Toxicology

Immunotoxicology

Immunoglobulin Responses to Experimental Silicosis

Shu-Hai Huang*, Ann F. Hubbs{dagger}, Charles F. Stanley*, Val Vallyathan{dagger}, Peter C. Schnabel*, Yongyut Rojanasakul*, Joseph K. H. Ma*, Daniel E. Banks* and David N. Weissman{dagger},1

* West Virginia University, Morgantown, West Virginia 26506; and {dagger} Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Analytical Services Branch, 1095 Willowdale Road, Morgantown, West Virginia 26505

Silicosis is a crippling fibrotic lung disease induced by inhalation of crystalline silica. One feature of silicosis is systemic and pulmonary immune dysfunction characterized in part by elevations in serum and bronchoalveolar lavage (BAL) immunoglobulins. A major specific aim of the current report was to demonstrate that an experimental model of silicosis previously well characterized for the development of pulmonary inflammation and fibrosis would also exhibit increased levels of serum and BAL IgG and IgM similar to those of human silicosis. We also sought to document the anatomic compartments responsible for these immunoglobulin responses. To address these specific aims, we compared levels of IgG and IgM in serum and BAL from rats with experimental silicosis induced by inhalation of silica with levels of these immunoglobulins in titanium dioxide (TiO2)- and sham (air)-exposed controls. The ability of mononuclear cell populations from lung, lung-associated lymph node, and spleen to produce IgG and IgM ex vivo were also compared. We found that experimental silicosis was associated with elevated IgG and IgM levels in blood and BAL relative to the control groups. Our findings also suggested that draining lung-associated lymph nodes (LALN) were the most important sites for increased IgG and IgM production in experimental silicosis, with lungs contributing to a lesser degree. Increased production in the LALN appeared related to marked expansion in total numbers, but not relative proportion, of B lymphocytes.

Key Words: silicosis; quartz; titanium dioxide; IgG; IgM; bronchoalveolar lavage; lymphocyte; rat.


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