ACUTE INFLAMMATORY ACTIVITY OF THE S100 PROTEIN CP-10 - ACTIVATION OFNEUTROPHILS IN-VIVO AND IN-VITRO

The murine S100 chemotactic protein of m.w. 10,000 termed (CP-10), has potent chemotactic activity for murine and human myeloid cells. We ex amined the ability of a synthetic CP-10 hinge region peptide CP-10((42 -55)) and rCP-10 to act as chemotactic agents and induce expression of the adhesion molecule Mac-1 (CD 11b/CD 18) in vivo. Maximal neutrophi l (PMN) accumulation occurred between 2 to 8 h after mouse footpad inj ection of rCP-10 (10(-7) M) or CP-10 peptide (10(-6) M). The infiltrat ing PMN expressed high levels of Mac-1, and low levels of the murine L -selectin Mel-14. Injection of CP-10 peptide i.p. also induced infiltr ation of PMNs that expressed high levels of Mac-1. Cell suspensions ob tained after i.p. injection of CP-10 peptide could be significantly in hibited from adhering to fibrinogen-coated plates when incubated with anti-Mac-1 antibody. The chemotactic activity of CP-10 peptide toward murine inflammatory PMN in vitro was also inhibited by anti-Mac-1 anti body. Neither CP-10 analogue stimulated or primed murine inflammatory or human blood neutrophils for superoxide production or granular enzym e release. The localization of CP-10 in vivo was examined using murine footpads injected with LPS and was found to be concentrated around th e endothelial cells of the small blood vessels. This distribution sugg ests that the accumulated CP-10 may contribute to the generation of a chemotactic gradient.