© 2003 American Thoracic Society DOI: 10.1165/rcmb.4883 Surfactant Protein A Inhibits Lipopolysaccharide-Induced In Vivo Production of Interleukin-10 by Mononuclear Phagocytes during Lung InflammationUnité de Défense Innée et Inflammation, Unité Associée Institut Pasteur/Institut National de la Santé et de la Recherche Médicale, U485, Paris, France; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Cincinnati, Cincinnati, Ohio Address correspondence to: Dr. Michel Chignard, Unité de Défense Innée et Inflammation, Unité Associée Institut Pasteur/Institut National de la Santé et de la Recherche Médicale, U485, 25 rue du Dr. Roux, 75015 Paris, France. E-mail: chignard{at}pasteur.fr We previously demonstrated that resident alveolar macrophages from naive mice do not synthesize interleukin (IL)-10, whereas mononuclear phagocytes (MP) recruited during the lung inflammatory process are transiently competent for IL-10 production when exposed to lipopolysaccharide (LPS) in vitro. As surfactant protein A (SP-A), a member of the collectin family, inhibits LPS-induced in vitro IL-10 formation by bone marrow–derived macrophages, we studied its effect on MP under in vivo inflammatory conditions. When mice with LPS-induced inflamed lungs were given a second intranasal LPS administration, IL-10 concentration recovered in the bronchoalveolar lavage fluids varied as a function of the time interval between the two LPS doses. Thus, IL-10 concentration increased with the number of MP up to Day 3, and then decreased to undetectable values within 24 h, despite a continued increase in the number of MP. Analysis of IL-10 mRNA from purified MP indicated that gene expression correlated with the IL-10 level in the bronchoalveolar lavage fluid. In contrast to IL-10 production, SP-A concentrations during LPS-induced inflammation decreased with a nadir at Day 3, and then increased significantly within 24 h. Furthermore, intranasal administration of exogenous SP-A to mice with LPS-induced inflamed lungs led to a repression of the IL-10 production. In summary, this study demonstrates for the first time an in vivo inhibitory role of SP-A on the anti-inflammatory activity of MP, through inhibition of IL-10 production.
Abbreviations: acethylcholinesterase, AchE • acute respiratory distress syndrome, ARDS • bronchoalveolar lavage fluid, BALF • enzyme-linked immunosorbent assay, ELISA • interleukin, IL • lipopolysaccharide, LPS • monoclonal antibody, mAb • mononuclear phagocytes, MP • phycoerythrin, PE • polymorphonuclear neutrophils, PMN • surfactant protein A, SP-A • solid phase immunoenzyme assay, SPIE-IA • tumor necrosis factor- This article has been cited by other articles:
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