Eur. J. Immunol. 1990. 20: 253-257
Jean-Marc Cavaillono, Catherine Fittingo and Nicole Haeffner-CavaillonA Unit6 d'Immuno-Allergic, Institut PasteurO and INSERM U28, H6pital Broussaisa, Paris
C5a enhances LPS-induced IL 1 and TNF release
253
Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide-stimulatedmonocytes and macrophages Lipopolysaccharide (LPS) is a potent inducer of interleukin 1(IL 1) synthesisand release, and of tumor necrosis factor (TNF) secretion. Many signals can enhance the LPS-induced production of these cytokines.We have previously observed that addition of low amounts of normal human serum to the culture medium enhances IL 1production. Among serum factors, anaphylatoxins C3a and C5a and/or their desArg derivatives have been shown to enhance LPS-induced IL 1 and TNF production. However, the capacity of natural anaphylatoxins to induce by themselves the production of cytokines remains a controversal issue. We have investigated the capacity of human recombinant C5a (hrC5a) to induce IL 1and TNF production. Despite its lack of direct triggering, hrC5a was able to act synergistically with LPS, leading to higher IL 1 and TNF release by human monocytes and mouse peritoneal macrophages. As assessed by the comitogenic assay, hrC5a increased IL 1release, whereas cell-associated IL 1activity was not significantlymodified. Measurement by enzyme-linked immunosorbent assay of human IL l p led to similar conclusions, whereas measurement of IL la by radioimmunoassay indicated, in addition, an increase in intracellular IL la.
1 Introduction
2 Materials and methods
LPS of Gram-negative bacteria is one of the most potent activatorsof monocytes and M a , and many of its biological activities are due to its capacity to trigger the production and release of IL 1 and TNF-a by monocytes/M
Jean-Marc Cavaillono, Catherine Fittingo and Nicole Haeffner-CavaillonA Unit6 d'Immuno-Allergic, Institut PasteurO and INSERM U28, H6pital Broussaisa, Paris
C5a enhances LPS-induced IL 1 and TNF release
253
Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide-stimulatedmonocytes and macrophages Lipopolysaccharide (LPS) is a potent inducer of interleukin 1(IL 1) synthesisand release, and of tumor necrosis factor (TNF) secretion. Many signals can enhance the LPS-induced production of these cytokines.We have previously observed that addition of low amounts of normal human serum to the culture medium enhances IL 1production. Among serum factors, anaphylatoxins C3a and C5a and/or their desArg derivatives have been shown to enhance LPS-induced IL 1 and TNF production. However, the capacity of natural anaphylatoxins to induce by themselves the production of cytokines remains a controversal issue. We have investigated the capacity of human recombinant C5a (hrC5a) to induce IL 1and TNF production. Despite its lack of direct triggering, hrC5a was able to act synergistically with LPS, leading to higher IL 1 and TNF release by human monocytes and mouse peritoneal macrophages. As assessed by the comitogenic assay, hrC5a increased IL 1release, whereas cell-associated IL 1activity was not significantlymodified. Measurement by enzyme-linked immunosorbent assay of human IL l p led to similar conclusions, whereas measurement of IL la by radioimmunoassay indicated, in addition, an increase in intracellular IL la.
1 Introduction
2 Materials and methods
LPS of Gram-negative bacteria is one of the most potent activatorsof monocytes and M a , and many of its biological activities are due to its capacity to trigger the production and release of IL 1 and TNF-a by monocytes/M
