Agonist and antagonist dual effect of the cross-linked S19 ribosomal protein dimer in the C5a receptor-mediated respiratory burst reaction of phagocytic leukocytes

Objective: To examine the behavior of the crosslinked dimer of S19 ribosomal protein (RP S19), a natural C5a receptor ligand, in the C5a receptor-mediated respiratory burst reaction of monocytes and neutrophils.Methods: The respiratory burst reaction of leukocytes was quantitatively observed by continuous spectrophotometric measurement of the reduction of a water-soluble tetrazolium salt, WST-1.Results: The RP S19 dimer induced the respiratory burst of monocytes, but not of neutrophils. Furthermore, in neutrophils, the RP S19 dimer inhibited the reaction induced by C5a, but did not affect the formyl-Met-Leu-Phe-induced reaction. The dimer of a deletion mutant at the C-terminal portion of the RP S19 induced a respiratory burst reaction similar to the one induced by C5a, both in monocytes and neutrophils. Inversely, a chimeric fusion protein between C5a and RPS19, consisting of the addition of the 12 C-terminal amino acid residues of RP S19 after the C-terminal Arg⁷⁴ of the C5a molecule, behaved similarly to the RP S19 dimer.Conclusions: The RP S19 dimer works as an agonist and antagonist of the C5a receptor in the monocyte and the neutrophil respiratory burst reactions, respectively. The switch moiety between the antagonist and agonist of the RP S19 dimer for the C5a receptor in the induction of respiratory burst of phagocytes localizes at the C-terminal region of RP S19.Received 27 August 2004; returned for revision 22 October 2004; accepted by M. Katori 28 October 2004