Long term iNOS expression in thoracic lymph nodes of silicotic rats.
Beside the lung, thoracic lymph nodes are most affected during silicosis. The mechanisms leading to enlargement of the lymph nodes and partial activation of lymph node cells are still unclear. The present study demonstrates an increase in iNOS mRNA expression in the lung draining lymph nodes of rats at 1, 2, and 8 months following silica exposure. Histopathological analysis revealed that iNOS protein was exclusively expressed by macrophages located within the granulomatous areas of the enlarged lymph nodes. In contrast, no differences in mRNA expression and number of iNOS-positive cells were found in the lungs of silica-exposed and non-exposed rats. In vitro experiments showed that silica particles alone did not induce NO release in primary alveolar macrophages (AMs) or the alveolar macrophage cell line NR8383. However, the addition of interferon (IFN)-gamma led to a significant nitric oxide production by primary AMs. NR8383 cells responded only when a combination of IFN-gamma and silica particles was applied. These results indicate that the macrophage activator IFN-gamma, which has already been shown to be expressed at elevated levels by lymphocytes of the silicotic lymph nodes, may be responsible for the long-lasting iNOS expression in thoracic lymph nodes. Our observations support the hypothesis that the mutual activation of lymphocytes and macrophages is a central process in the development of chronic silicosis.
Institute of Immunology, Philipps University, Marburg, Germany.
Anke
A
Friedetzky
Veronika
V
Grau
Marc
M
Wieckenberg
Anja
A
Lewen
Diethard
D
Gemsa
Holger
H
Garn
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000201:enzymology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011916:Rats, Inbred F344; D012829:Silicosis / Q000201:enzymology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat