REGULATION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 GENE-EXPRESSION AND SECRETION IN RAT PULMONARY ALVEOLAR MACROPHAGES BY LIPOPOLYSACCHARIDE,TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERLEUKIN-1-BETA

Chemotactic cytokines coordinate the recruitment of leukocytes into th e lung during pulmonary inflammation. In a previous study, we determin ed that rat pulmonary alveolar macrophages (PAMs) facilitate monocyte recruitment and activation in the lung during acute inflammatory lung injury, in part, through the inducible expression of monocyte chemoatt ractant protein-1 (MCP-1). MCP-1 is an 11 to 15 kD basic peptide that specifically mediates monocyte chemotaxis and activation. Inflammatory mediators that regulate the expression and secretion of MCP-1 by rat PAMs have not been identified. We determined that stimulation of resid ent rat PAMs with bacterial lipopolysaccharide (LPS), murine tumor nec rosis factor-alpha, or human interleukin-1 beta resulted in the induci ble expression of MCP-1 mRNA and the secretion of biologically active MCP-1. In contrast, phorbol myristate acetate, a nonphysiologic leukoc yte activator, was significantly less effective in stimulating either enhanced MCP-1 mRNA expression or secretion of MCP-1. These results in dicate that the expression of MCP-1 mRNA and the secretion of MCP-1 by rat PAMs are regulated by bacterial products (LPS) and inflammatory c ytokines. Further, these results suggest that resident PAMs, through e laboration of MCP-1, may play a pivotal role in regulating recruitment and activation of monocytes in the lung during acute inflammatory lun g injury.