MCP-1 EXPRESSION BY RAT TYPE-II ALVEOLAR EPITHELIAL-CELLS IN PRIMARY CULTURE

Recruitment and activation of mononuclear phagocytes are potentially c ritical regulatory events for control of pulmonary inflammation. Locat ed at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recrui tment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of mon ocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murin e JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was incre ased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP- 1 Ag into the apical compartment by both control and IL-1-stimulated c ells as measured by specific MCP-1 ELISA. Northern blot analysis revea led that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose -dependent manner, whereas dexamethasone blocked MCP-1 expression by c ells stimulated with IL-1. In contrast to previous results using trans formed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alv eolar epithelial cells may have an important and previously unrecogniz ed role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through t he production of MCP-1.