INDUCTION OF MONOCYTE CHEMOTACTIC PROTEINS MCP-1 AND MCP-2 IN HUMAN FIBROBLASTS AND LEUKOCYTES BY CYTOKINES AND CYTOKINE INDUCERS - CHEMICAL SYNTHESIS OF MCP-2 AND DEVELOPMENT OF A SPECIFIC RIA

Monocyte chemotactic proteins (MCP) belong to a group of structurally and functionally related factors, called chemokines. To facilitate add itional characterization of the recently identified MCP-2, the 76-resi due protein was chemically synthesized. The synthetic 7-kDa monomeric protein was chemotactic for monocytes at 1 nM and was biochemically si milar to natural MCP-2. Sensitive radioimmunoassays for both MCP-1 and MCP-2 were developed. These RIAs were specific in that no cross-react ivity could be observed, and other chemokines or cytokines were not de tected. Induction of MCP-1 and MCP-2 in human diploid fibroblasts and peripheral blood leukocytes as well as osteosarcoma, epidermal carcino ma, and melanoma cells by the cytokines IL-1 beta, IFN-beta, and IFN-g amma and cytokine inducers such as dsRNA, virus, endotoxin, mitogen, a nd phorbol ester was studied. In connective tissue cells, IL-1 beta wa s the best inducer of MCP-1, but IFN-gamma was a superior inducer of M CP-2. Mononuclear cells also proved to be a source of MCP-1 and MCP-2 when stimulated by most of the inducers tested. Granulocytes, however, were inefficient producers. Measles virus induced MCP-1 and MCP-2 in most cell types. In general, the yields of MCP-2 were at least 10-fold lower than those of MCP-1. It is concluded that, although MCP-2 is of ten coproduced with MCP-1, regulation of expression of the two chemoki nes is not identical. It remains to be studied under which pathologica l conditions MCP-2 is released in vivo and whether MCP-1 and MCP-2 can activate different target cells.