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 additional characterization of the recently identified MCP-2, the 76-residue protein was chemically synthesized. The synthetic 7-kDa monomeric protein was chemotactic for monocytes at 1 nM and was biochemically similar to natural MCP-2. Sensitive radioimmunoassays for both MCP-1 and MCP-2 were developed. These RIAs were specific in that no cross-reactivity could be observed, and other chemokines or cytokines were not detected. Induction of MCP-1 and MCP-2 in human diploid fibroblasts and peripheral blood leukocytes as well as osteosarcoma, epidermal carcinoma, and melanoma cells by the cytokines IL-1 beta, IFN-beta, and IFN-gamma and cytokine inducers such as dsRNA, virus, endotoxin, mitogen, and phorbol ester was studied. In connective tissue cells, IL-1 beta was the best inducer of MCP-1, but IFN-gamma was a superior inducer of MCP-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 often coproduced with MCP-1, regulation of expression of the two chemokines is not identical. It remains to be studied under which pathological conditions MCP-2 is released in vivo and whether MCP-1 and MCP-2 can activate different target cells.
Van Damme
J
J
Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Belgium.
Proost
P
P
Put
W
W
Arens
S
S
Lenaerts
J P
JP
Conings
R
R
Opdenakker
G
G
Heremans
H
H
Billiau
A
A
D002478:Cells, Cultured; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000032:analysis / Q000096:biosynthesis* / Q000138:chemical synthesis; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins; D011863:Radioimmunoassay
C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins