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 x 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.
Department of Molecular Pathology, Kumamoto University, Japan.
Yuuichiro
Y
Oda
Kazutaka
K
Tokita
Yoshihiko
Y
Ota
Ying
Y
Li
Keisuke
K
Taniguchi
Norikazu
N
Nishino
Katsumasa
K
Takagi
Tetsuro
T
Yamamoto
Hiroshi
H
Nishiura
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015936:Complement C5a / Q000737:chemistry*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012710:Serum Albumin, Bovine / Q000737:chemistry
D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D012710:Serum Albumin, Bovine; D015936:Complement C5a