Agonistic and Antagonistic Effects of C5a-Chimera Bearing S19 Ribosomal Protein Tail Portion on the C5a Receptor of Monocytes and Neutrophils, Respectively

C-terminus of S19 ribosomal protein (RP S19) endows the cross-linked homodimer with a dual effect on the C5a receptor in leucocyte chemoattraction; agonistic effect on the monocyte receptor, and antagonistic effect on the neutrophil receptor. C5a exhibits the uniform agonistic effect on this receptor of both cell types. We have currently prepared a recombinant C5a-chimeric protein bearing the C-terminus of RP S19 (C5a/RP S19 chimera) to be used as a substitute of the RP S19 dimer. In vitro, this chimera similarly inhibited the intracellular Ca 2+ mobilization of neutrophils induced by C5a to the RP S19 dimer did. In the guinea pig skin, 10 −7 M C5a/RP S19 chimera exhibited an inhibitory capacity to the neutrophil infiltration induced by 3 × 10 −7 M C5a without enhancing monocyte infiltration. In reverse passive Arthus reaction, the neutrophil infiltration associated with plasma extravasation was significantly reduced by the simultaneous administration of 10 −7 M C5a/RP S19 chimera with antibodies. The C5a/RP S19 chimera is a useful tool not only to examine the molecular mechanism that underlies the functional difference of the C5a receptor between monocytes and neutrophils, but also to prevent C5a-mediated hyper-response of neutrophils in acute inflammation.