A Biphasic Response to Silica: I. Immunostimulation Is Restricted to the Early Stage of Silicosis in Lewis Rats

• Published in: American journal of respiratory cell and molecular biology Vol. 30; no. 6; pp. 823 - 829
• Main Authors: Langley, Raymond J, Kalra, Roma, Mishra, Neerad C, Hahn, Fletcher F, Razani-Boroujerdi, Seddigheh, Singh, Shashi P, Benson, Janet M, Pena-Philippides, Juan Carlos, Barr, Edward B, Sopori, Mohan L
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.06.2004; American Thoracic Society
• Subjects: Animals; Brain Chemistry; Bronchoalveolar Lavage Fluid - chemistry; Disease Models, Animal; Immune System - physiology; Lung - cytology; Lung - metabolism; Lung - pathology; Male; Particle Size; Rats; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Silicon Dioxide - chemistry; Silicon Dioxide - immunology; Silicon Dioxide - metabolism; Silicosis - immunology; Silicosis - metabolism; Silicosis - pathology; Spleen - chemistry; Spleen - cytology; Spleen - metabolism
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2003-0284OC

Inhalation of crystalline silica may lead to acute or chronic silicosis. Although chronic silicosis is associated with increased incidence/exacerbation of autoimmune disorders, the immunologic effects of chronic silicosis are not completely understood. In an animal model of chronic silicosis, Lewis rats were exposed to filtered air or silica (1.75 microm average particle size) at an exposure concentration of 6.2 mg/m(3), 6 h/d, 5 d/wk for 6 wk, and observed up to 27 wk after the exposure. Based on silica burden, lung histopathology, and immunologic changes, two distinct stages were identified in the development of chronic silicosis. Stage 1 (4-28 d after exposure) was characterized by silica deposition in various tissues, and augmented antibody and cellular immunity. Although bronchoalveolar lavage contained an increased number of activated macrophages, protein and lactate dehydrogenase levels were comparable to controls. In Stage 2 (>/= 10 wk), silica was localized in epithelioid macrophages, and T cell immunity had returned to normal, but the lavage fluids contained increased protein concentration and lactate dehydrogenase activity. Moreover, lungs from silica-treated animals contained neutrophils and lymphocytes, and exhibited granulomatous changes around the silica-containing epithelioid macrophages. Thus, in the early stages of silicosis, silica activates the immune system; however, the progression of lung granulomas does not depend on a continually activated adaptive immune system.