Role of Pasteurella multocida, Pasteurella haemolytica and Salmonella typhimurium porins on inducible nitric oxide release by murine macrophages

The aim of this study was to verify whether Pasteurella haemolytica, P. mul tocida and Salmonella typhimurium porins could affect the inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release by murine re sident peritoneal macrophages in vitro. We also compared their effect with that elicited by P. haemolytica, P, multocida and S. typhimurium lipopolysa ccharide (LPS) whose biological activity is well known. Variations in NO re lease and NOS mRNA expression due to variable concentrations of porins were recorded and compared. We also investigated the synergism between bacteria l products and interferon gamma (IFN-gamma). With this aim cells were incub ated with porins together with murine rIFN-gamma prior to assessing the pre sence of NO in the supernatant and mRNA analysis. Porins in themselves were not able to induce NO release by resident peritoneal macrophages. Incubati on of macrophages with IFN-gamma in the presence of porins increased NO rel ease, whereas incubation in the presence of the arginine analog N-G-monomet hyl-L-arginine (NMA) inhibited NO release. The greatest NO release was obta ined using porins at a concentration of 5 mu g/mL. Porins, together with IF N-gamma, were also able to upregulate the mRNA expression of iNOS. Our find ings suggest that Gram-negative porins are able to modulate inflammatory an d immunological responses by affecting the release of NO and the expression of iNOS gene in activated macrophages. (C) 2000 Editions scientifiques et medicales Elsevier SAS.