INDUCTION OF THE S100 CHEMOTACTIC PROTEIN, CP-10, IN MURINE MICROVASCULAR ENDOTHELIAL-CELLS BY PROINFLAMMATORY STIMULI

Microvascular endothelial cells (EC) have multiple functions in inflam matory responses, including the production of chemoattractants that en hance leukocyte transmigration into tissues. Chemotactic protein, 10 k D (CP-10), is an S100 protein with potent chemotactic activity for mye loid cells in vitro and in vivo and is expressed in neutrophils and li popolysaccharide (LPS)-activated macrophages. We show here that CP-10 is induced in murine endothelioma cell lines (bEnd-3. sEnd-1. and tEnd -1) after activation with LPS and interteukin-1 (IL-1) but not tumor n ecrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma). Indu ction was not mediated by endogenous release of IL-1 or TNF alpha and was not directly upregulated by phorbol myristate acetate, calcium ion ophore, or vitamin D3. EC were exquisitely sensitive to IL-1 activatio n (3.4 U/mL) and CP-10 mRNA induction with IL-1 occurred earlier (8 ho urs) than with LPS (12 hours). Furthermore, some microvessels and capi llaries in delayed-type hypersensitivity lesions expressed cytoplasmic CP-10. Responses to LPS and not II-1 in vitro were regulated by the d egree of cell confluence and by TNF alpha costimulation. The related M RP14 mRNA had a different induction pattern. Monomeric and homodimeric CP-10 upregulated by activation was predominantly cell-associated. EC -derived CP-10 may contribute to amplification of inflammatory process es by enhancing leukocyte shape changes and transmigration in the micr ocirculation. (C) 1997 by The American Society of Hematology.