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Involvement of the membrane form of tumour necrosis factor‐&agr; in lipopolysaccharide‐induced priming of mouse peritoneal macrophages for enhanced nitric oxide response to lipopolysaccharide
Author(s) -
ANCUTA P.,
FAHMI H.,
PONS J. F.,
LE BLAY K.,
CHABY R.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00338.x
Subject(s) - lipopolysaccharide , priming (agriculture) , pentoxifylline , tumor necrosis factor alpha , cytokine , nitric oxide , biology , immunology , pharmacology , endocrinology , botany , germination
We studied the pathways of macrophage response to lipopolysaccharide (LPS). When mouse macrophages pre‐exposed to LPS were restimulated with this agent, reduced tumour necrosis factor‐&agr; (TNF‐&agr;) responses (desensitization/endotoxin tolerance) were accompanied by increased (priming) nitric oxide (NO) responses. Priming was also inducible with recombinant interferon‐&bgr; (IFN‐&bgr;). The requirement of TNF‐&agr; biosynthesis in the LPS‐induced priming was also suggested by the observation that both anti‐TNF‐&agr; serum and pentoxifylline inhibited this effect. However, addition of mouse recombinant TNF‐&agr; (mrTNF‐&agr;) did not enhance the priming induced by LPS or IFN‐&bgr;, and preincubation with mrTNF‐&agr; alone, or in association with other cytokines produced by macrophages (interleukin‐1&bgr;, interleukin‐6, or leukaemia inhibitory factor), did not induce a priming effect. We found however, that pentoxifylline, which blocked the priming, also decreased the level of membrane‐bound TNF‐&agr;. Furthermore, exposure to compound BB‐3103 (a metalloproteinase inhibitor that blocks the processing of membrane‐bound TNF‐&agr; yielding to the secreted cytokine) enhanced the priming effect, the expression of membrane TNF‐&agr; and the specific binding of LPS. These observations suggest that the membrane form of TNF‐&agr; is involved in the interaction of LPS with a receptor required for LPS‐induced priming.