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  • Title: Trace levels of bacterial lipopolysaccharide prevent interferon-gamma or tumor necrosis factor-alpha from enhancing mouse peritoneal macrophage respiratory burst capacity.
    Author: Ding AH, Nathan CF.
    Journal: J Immunol; 1987 Sep 15; 139(6):1971-7. PubMed ID: 3040860.
    Abstract:
    Preexposure of resident mouse peritoneal macrophages for 1 hr to traces of bacterial lipopolysaccharide (LPS) (less than or equal to 1 ng/ml) rendered the cells refractory to activation by recombinant interferon-gamma (rIFN gamma) or recombinant tumor necrosis factor-alpha (rTNF alpha), as evaluated by release of H2O2 upon stimulation with phorbol myristate acetate. Inhibition persisted for at least 4 days. Fifty percent inhibition of activation mediated by rIFN gamma followed 1 hr exposure to 10 pg/ml LPS. Fifty percent inhibition of activation mediated by rTNF alpha was achieved with 1 hr exposure to 1 pg/ml LPS. Such low levels LPS exposures (concentration X time) are far below those reported for many other actions of LPS on host cells. Inhibition was partially prevented by the cyclooxygenase inhibitors indomethacin, ibuprofen, and acetylsalicylic acid. Exogenous prostaglandins PGE1 and PGE2, and the 3',5'-cyclic adenosine monophosphate analog dibutyryl cyclic adenosine monophosphate (cAMP), mimicked the inhibitory effect of LPS in a dose-dependent manner, consistent with the hypothesis that formation of endogenous cyclooxygenase products in response to LPS may elevate intracellular cAMP and that the latter may mediate the observed inhibition. In addition, neutralizing antibody against IFN alpha and IFN beta selectively prevented LPS inhibition of activation mediated by rIFN gamma, but not by rTNF alpha. This suggests that IFN alpha and/or IFN beta induced by LPS also contributed to inhibition of activation by rIFN gamma. Thus, release of LPS may afford microorganisms a means by which to interfere with immunologically mediated enhancement of the respiratory burst-dependent antimicrobial capacity of macrophages.
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