IN-VIVO EXPOSURE TO PORPHYROMONAS-GINGIVALIS UP-REGULATES NITRIC-OXIDE BUT SUPPRESSES TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY CULTURED MACROPHAGES

The present study was designed to test whether the functional response of mouse macrophages elicited by chronic exposure to bacteria will be different from that of cells elicited by a nonbacterial irritant. Mac rophage elicitation was conducted by Porphyromonas gingivalis, a major periodontal pathogen, in comparison to a standard elicitation by thio glycollate (TG). We measured lipopolysaccharide (LPS)-induced nitric o xide (NO) and tumour necrosis factor-alpha (TNF-alpha) secretion by th e elicited macrophages, and the expression of inflammatory cytokines i n the whole elicited cell population. In addition, we tested the respo nse of TG-elicited macrophages to pretreatment with P. gingivalis LPS in vitro, Mouse peritoneal macrophages were harvested 4 days after int raperitoneal injection of TC or heat-killed P. gingivalis. TG-elicited macrophages produced undetectable levels of TNF-alpha and approximate ly 0.5 mu m of NO. The stimulation of the macrophages with LPS resulte d in the secretion of NO and TNF-alpha in a dose-dependent manner. The P. gingivalis-elicited macrophages produced basal levels of approxima tely 5 mu M NO, but TNF-alpha was not detectable. LPS stimulation of t hese cells further increased the secretion of NO eightfold while TNF-a lpha remained undetectable. The NO secretion by P. gingivlais-elicited cells was significantly higher than that by TG-elicited cells. Examin ation of cytokine expression in the whole elicited cell population rev ealed that both P. gingivalis-elicited cells and TG-elicited cells exp ressed messenger RNA for interleukin-2 (IL-2), TNF-alpha and interfero n-gamma (IFN-gamma), but not for IL-4. IL-6 was expressed in P. gingiv alis-elicited cells only. Pretreatment of TG-elicited macrophages with P. gingivalis LPS for 24 hr prior to a second LPS challenge resulted in downregulation of TNF-alpha secretion and up-regulation of NO secre tion, a response similar to that seen in P. gingivalis-elicited perito neal macrophages. The results suggest that the in vivo exposure of res ident macrophages to P. gingivalis induces functional changes in perit oneal macrophages. These changes might be due to the effect of P. ging ivalis LPS.