title: Time course of chemotactic factor generation and the corresponding macrophage response to asbestos inhalation.
abstract: Inhalation of asbestos fibers causes a progressive fibrotic lung disease in humans and animals. Pulmonary macrophages are associated with asbestos exposure and have been implicated as significant mediators of the pathogenic process. In previous studies, we showed that macrophages are attracted to sites of asbestos fiber deposition, i.e., alveolar duct bifurcations. We also showed that macrophages accumulated at these sites as the result of asbestos-induced activation of complement proteins on alveolar surfaces, consequently producing C5a, a chemotactic factor for macrophages. In the present study, we have demonstrated the time course of chemotactic factor generation and the corresponding macrophage response in vivo. A complement-dependent chemotactic factor for macrophages was activated during a 3-h exposure to asbestos and reached maximal activity by 3 h postexposure. Macrophage accumulation followed and reached a maximal amount by 24 h postexposure. Rats decomplemented with cobra venom factor exhibited a significant reduction in macrophage accumulation, but the macrophage response ensued when serum complement returned to normal. Approximately 30% of the macrophages lavaged from complement-normal, asbestos-exposed animals contained fibers, whereas only half as many macrophages from decomplemented rats contained asbestos. A small but significant increase in lavaged lung protein was measured in asbestos-exposed animals. Evidence supports the concept that complement proteins on alveolar surfaces are derived from normal transudation of serum components from the pulmonary vasculature. Increased serum transudation could provide a source of alveolar complement that sustains the generation of a chemotactic factor for macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001194:Asbestos; D001195:Asbestosis / Q000276:immunology*; D002630:Chemotactic Factors / Q000276:immunology*; D003167:Complement Activation; D003182:Complement C5 / Q000276:immunology*; D015936:Complement C5a; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D008168:Lung / Q000648:ultrastructure; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D013997:Time Factors
chemical_list: D002630:Chemotactic Factors; D003182:Complement C5; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D001194:Asbestos; D015936:Complement C5a