IFN-γ up-regulates the human C5a receptor (CD88) in myeloblastic U937 cells and related cell lines

On human mature monocytes the immunomodulator IFN-γ has been shown to down-regulate the receptor for the anaphylatoxic peptide C5a (CD88, C5aR). In this study, we show that in immature myelo-/monoblastic U937, HL60, and MonoMac6 cells, IFN-γ induces C5aR-ligand binding activity. In U937 cells, this induction cannot be blocked by the protein kinase C inhibitor staurosporine. An increase in free cytosolic Ca²⁺ upon ligand binding indicates functional coupling of this receptor in U937 and HL-60 cells. G- Proteins involved in this C5a responsiveness after IFN-γ induction are completely pertussis toxin sensitive. Our data suggest that an additional pertussis toxin-resistant pathway exists in U937 cells after induction by dibutyryl cAMP. However, this is not due to changes in the mRNA level of the pertussis toxin-insensitive G-protein subunit Gα₁₆. Induction by dibutyryl cAMP, but not that by IFN-γ, resulted in C5a-dependent release of N-acetyl- β-D-glucosaminidase, further highlighting functional differences in the effects of the inducers. Our data show an IFN-γ-dependent increase in C5aR expression and suggest a maturation-related change in signaling of the C5aR, presumably at the level of receptor coupling.