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IDENTIFICATION OF A CHEMOTACTIC DOMAIN OF THE PRO-INFLAMMATORY S100 PROTEIN CP-10


Lackmann, M; RAJASEKARIAH, P; LISMAA, SE; Jones, G; CORNISH, CJ; HU, SP; Simpson, RJ; Moritz, RL; GECZY, CL
1993-04-01
JOURNAL OF IMMUNOLOGY
Journal Article
150
7
2981-2991
We previously reported the purification and partial amino acid sequence of a novel murine cytokine designated CP-10, which has chemotactic activity for murine polymorphonuclear cells (PMN) and macrophages. The complete cDNA encoding an 88-amino acid polypeptide has been isolated and the sequence is presented here. Transient transfection of CP-10 cDNA into CV-1 cells confirmed the chemotactic activity of rCP-10 for murine PMN. CP-10 has sequence homology with members of the S100 family of Ca2+-binding proteins with pronounced amino acid sequence similarities within the putative N- and C-terminal Ca2+-binding sites, but differences within their connecting hinge and C-terminal regions. We have confirmed the hypothesis of Kligman and Hilt that functional specificity of individual members of the S100 protein family may reside in the hinge region. A synthetic peptide corresponding to the hinge region of CP-10 (CP-10(42-55)) was compared with native CP-10 in chemotaxis and skin test assays. Native CP-10 had potent activity for phagocytic cells, but not lymphocytes, in vitro (optimal activity, 10(-11) to 10(-13) M) and elicited a sustained recruitment of neutrophils and mononuclear cells over 24 h in vivo. The hinge-region peptide had strong chemotactic activity for murine phagocytic cells (optimal activity, 10(-10)-10(-11) M) but elicited only a transient infiltration of neutrophils over 4 to 8 h after intradermal injection. Results indicate that although the hinge region contributes significantly to the functional specificity of the S100 protein CP-10, sustained cellular recruitment typical of a delayed type hypersensitivity response is apparently dependent on the structural integrity of the protein.
AMER ASSOC IMMUNOLOGISTS
CALCIUM-BINDING PROTEIN; AMINO-ACID-SEQUENCE; PROCOAGULANT-INDUCING FACTOR; CELL-MEDIATED-IMMUNITY; CYSTIC-FIBROSIS; S-100 PROTEIN; HYPERSENSITIVITY REACTIONS; FIREFLY LUCIFERASE; MOLECULAR-CLONING; MESSENGER-RNA
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Creation Date 1993-04-01 12:00:00