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Antigen-Presenting Cell Population Dynamics during Murine Silicosis

¹ Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana

Correspondence and requests for reprints should be addressed to Celine Ann Beamer, Ph.D., Center for Environmental Health Sciences, Dept. of Biomedical and Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, 32 Campus Drive, Skaggs Building Room 155, University of Montana, Missoula, MT 59812-1552. E-mail: celine.beamer{at}umontana.edu

Silicosis is an occupational lung disease resulting from the inhalation of silica particles over prolonged periods of time, which causes chronic inflammation and progressive pulmonary fibrosis. Alveolar macrophages (AM) are critical effector cells, while less is known about the role and function of pulmonary dendritic cells (DC) in silicosis. We hypothesize that a balance exists between the suppressive nature of AM and the stimulatory capacity of DC to regulate lung immunity, and that this equilibrium may be overcome by silica exposure in vivo. Our results demonstrate that in response to silica exposure, both the percent and absolute number of AM significantly decreased over time, with a concomitant significant increase in DC. Both AM and DC exhibited cellular activation in response to silica, indicated by increased expression of cell surface markers. In the absence of silica-induced AM apoptosis (TNFR 1/2–null and Gld mice), no change was observed in the percent or absolute number of either cell type. Furthermore, bone marrow–derived DC, but not bone marrow–derived macrophages, migrated from the alveoli into the lung parenchyma in response to silica, resulting in significantly increased numbers of activated T lymphocytes. Collectively, the results demonstrate that AM and DC are distinct antigen-presenting cells within the respiratory tract that respond to silica exposure in vivo in unique ways, with significant implications for immune reactivity of the lung in response to environmental pathogens.

Key Words: alveolar macrophage • pulmonary dendritic cell • silica • activation • inflammation

CLINICAL RELEVANCE Little is known about the role and function of dendritic cells (DC) in silicosis. Our results show that DC respond to silica in unique ways, suggesting a previously unrecognized role in the immune reactivity of the lung to environmental particles.

 

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