Anaphylatoxins C5a and C3a induce nuclear factor kappa B activation in human peripheral blood monocytes

The anaphylatoxins C5a and C3a are involved in the regulation of cytokine p roduction. In this study the capability of C5a and C3a to induce transcript ion factor activation was examined. C5a and C3a stimulation of human periph eral blood monocytes resulted in nuclear expression of a DNA binding activi ty with specificity to the kappa B sequence. The p50 and p65 proteins, cons tituents of the prototypic nuclear factor kappa B, were identified as compo nents of the DNA-protein complexes by anti-peptide antibodies in gel supers hift assays. C5a induced kappa B binding activity was detected 15 min after agonist stimulation, peaked at 30-40 min, and remained detectable at 2 h. Binding to kappa B sequence was accompanied by an initial decrease and subs equent increase in the cytoplasmic I kappa B alpha levels, as detected by W estern blotting using an anti-I kappa B alpha antibody. Pertussis toxin tre atment markedly decreased kappa B binding activities induced by both C5a an d C3a, whereas cholera toxin displayed no inhibitory effect. Neither of the two toxins affected kappa B binding activity induced by TNF alpha in the s ame cells. These results imply a potential role of the anaphylatoxins C5a a nd C3a in regulating leukocytes gene expression through G protein-coupled t ranscription factor activation. (C) 1998 Elsevier Science B.V. All rights r eserved.