Induction of monocyte chemoattractant protein-1 (MCP-1) production by Pseudomonas nitrite reductase in human pulmonary type II epithelial-like cells

Monocyte chemoattractant protein-1 (MCP-1), a chemoattractant for monocytes , is presumed to play a pivotal role in the recruitment and accumulation of monocytes in various diseases including pulmonary infections. We examined here whether or not Pseudomonas nitrite reductase (PNR), a recently identif ied IL-8 inducer in various respiratory cells, could stimulate human pulmon ary type II epithelial-like cells (A549) to induce MCP-1 production. A time - and dose-dependent induction of MCP-1 protein synthesis associated with a n increase of MCP-1 mRNA expression by A549 cells was observed in response to PNR. New protein translation was not required for PNR-mediated MCP-1 mRN A expression in the same cells. When anti-human MCP-1 monoclonal antibody w as used for neutralizing of monocyte chemotactic factor (MCF) activities in the culture supernatants of these cells stimulated with PNR, significant r eductions of MCF activities (the mean reduction rate; 49-59%, P<0.05) were observed. These data suggest that PNR may contribute to monocyte migration, through inducing pulmonary epithelial cell-derived MCP-1 production in the airway of patients with pneumonia due to P. aeruginosa. (C) 2000 Academic Press.