PREEXPOSURE OF MOUSE PERITONEAL-MACROPHAGES TO LIPOPOLYSACCHARIDE ANDOTHER STIMULI ENHANCES THE NITRIC-OXIDE RESPONSE TO SECONDARY STIMULI

The aim of this study was to compare the regulation of the production of tumor necrosis factor-alpha (TNF-alpha) and secondary nitric oxide (NO) in macrophages submitted to a sequence of two stimulations. Pre-e xposure for 18 h of mouse thioglycollate-elicited peritoneal macrophag es to low doses (1-10 ng/ml) of lipopolysaccharide (LPS), in the prese nce or absence of serum, induces on one hand a desensitization (endoto xin tolerance) for secondary TNF-alpha responses to LPS and, on the ot her hand, a 4 fold increase (priming) of secondary NO responses. Preex posure to components from Gram-positive bacteria (lipoteichoic acid, p eptidoglycan) and to a synthetic lipid structurally related to lipid A (compound M4), induced similar effects. In contrast to the desensitiz ation for TNF-alpha secretion, the priming for NO production was nor m imicked by sodium nitroprusside, a generator of NO. The results sugges t that concomitant but distinct activation pathways induced by LPS and other agents can be dissociated by serum-independent modulation proce sses elicited by preexposure of the cells to LPS itself, or to other s timuli.