Subchronic silica exposure enhances respiratory defense mechanisms and thepulmonary clearance of Listeria monocytogenes in rats

Both Listeria monocytogenes infection and silica exposure have been shown t o significantly alter immune responses. In this study, we evaluated the eff ect of preexposure to silica on lung defense mechanisms using a rat pulmona ry L. monocytogenes infection model. Male Sprague-Dawley rats were instille d intratracheally with saline ( vehicle control) or silica using either an acute treatment regimen (5 mg/kg; 3 days) or a subchronic treatment protoco l (80 mg/kg; 35 days). At 3 or 35 days after silica instillation, the rats were inoculated intratracheally with either similar to 5000 or 500,000 L. m onocytogenes. At 3, 5, and 7 days postinfection, the left lung was removed, homogenized, and cultured on brain heart infusion agar at 37 degreesC. The numbers of viable L. monocytogenes were counted after an overnight incubat ion. Bronchoalveolar lavage (BAL) was performed on the right lungs, and BAL cell differentials, acellular lactate dehydrogenase (LDH) activity and alb umin content were determined. Alveolar macrophage (AM) chemiluminescence (C L) and phagocytosis were assessed as a measure of macrophage function. Lung -associated lymph nodes were removed, and lymphocytes were recovered and di fferentiated. Preexposure to silica significantly increased the pulmonary c learance of L. monocytogenes as compared to saline controls. Exposure to si lica caused significant increases in BAL neutrophils, LDH and albumin, and lymph-nodal T cells and natural killer (NK) cells in infected and noninfect ed rats. CL and phagocytosis were also elevated in silica-treated rats. In summary, the results demonstrated that exposure of rats to silica enhanced pulmonary immune responses, as evidenced by increases in neutrophils, NK ce lls, T lymphocytes, and macrophage activation. These elevations in pulmonar y immune response are likely responsible for the increase in pulmonary clea rance of L. monocytogenes observed with preexposure to silica.