S19 ribosomal protein cross-linked dimer causes monocyte-predominant infiltration by means of molecular mimicry to complement C5a.
S19 ribosomal protein is a component of the protein-producing machinery, ribosome. When recombinant S19 proteins were cross-linked intermolecularly by plasma transglutaminase (coagulation factor XIIIa), this homodimer newly exhibited monocyte chemotactic activity. This effect was specific to monocytes. The S19 protein homodimer shared the immunoreactivity with the complement-derived chemotactic factor, component 5a (C5a). Monocytes pretreated with an anti-C5a receptor antibody or with a synthetic C5a receptor antagonist responded poorly in chemotaxis to this homodimer. These data indicate that the S19 protein homodimer possesses a 3-dimensional structure similar to C5a in terms of the immunologic epitope and the receptor ligand, although homology between their primary structures is only 4%. In contrast, the S19 protein homodimer did not attract polymorphonuclear leukocytes. In addition, the homodimer inhibited a chemotactic response of polymorphonuclear leukocytes to C5a in vitro and in vivo as a receptor antagonist. Furthermore, the S19 protein homodimer competitively inhibited the binding of radiolabeled C5a to polymorphonuclear leukocytes. The S19 protein homodimer with these opposite effects in the leukocyte chemotaxis seems to induce the monocyte/macrophage predominant infiltration in chronic inflammation.
Nishiura
H
H
Division of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Shibuya
Y
Y
Yamamoto
T
T
D000818:Animals; D001667:Binding, Competitive; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003001:Cloning, Molecular; D015936:Complement C5a / Q000737:chemistry* / Q000378:metabolism*; D003432:Cross-Linking Reagents; D019281:Dimerization; D004926:Escherichia coli; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000378:metabolism*
D003432:Cross-Linking Reagents; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D015936:Complement C5a