INDUCTION OF THE CHEMOTACTIC S100 PROTEIN, CP-10, IN MONOCYTE-MACROPHAGES BY LIPOPOLYSACCHARIDE

The murine S100 protein CP-10 is a potent chemotactic factor for murin e and human myeloid cells in vivo and in vitro. This is the first repo rt describing regulation of the CP-10 gene by a proinflammatory stimul us, lipopolysaccharide (LPS), in cells of the monocyte/macrophage line age. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells pree xposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. Th is was accompanied by increasing levels of cell-associated and release d CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 m RNA in elicited peritoneal macrophages, whereas mRNA and protein level s decreased following LPS challenge. The state of macrophage different iation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expressio n was controlled at the transcriptional level and nuclear run-on and p rotein synthesis inhibition assays indicated that LPS priming and chal lenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not ind uced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gr am-negative bacterial infection. (C) 1996 by The American Society of H ematology.