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MCP-1

This term has multiple meanings:


(-1-) monocyte chemoattractant protein-1

called also monocyte chemotactic protein-1. MCP-1 is encoded by the human JE gene at chromosome 17q11.2-q21.1, known also as SCYA2 (small inducible cytokine A2) (the factor has been renamed CCL2; see also: SCY family of cytokines for a systematic nomenclature of this factor). Antibodies directed against murine MCP-1 cross-react with the human factor. The human factor is 49 amino acids shorter at the aminoterminus than the rodent factor.

MCP-1 belongs to the family of chemotactic cytokines known as Chemokines. It is identical with MCAF (monocyte chemotactic and activating factor), MCP (monocyte chemotactic protein), HC11, SMC-CF (smooth muscle cell chemotactic factor), LDCF (lymphocyte-derived chemotactic factor), GDCF (glioma-derived monocyte chemotactic factor), TDCF (tumor-derived chemotactic factors) and P6. MCP-1 shows a high degree of homology with MARC protein. For a bioactive peptide fragment of MCP-1 that inhibits the chemotactic response of cells elicited by a wide range of chemokines see: peptide 3.

Weber et al (1996) have reported that MCP-1(2-76), an MCP-1 variant with a deletion of the aminoterminal amino acid, is active on eosinophils, whereas the parent factor is not. The deletion mutant has a markedly decreased activity on basophils as compared to the parent molecule. MCP-1(3-76) is completely inactive on eosinophils and basophils. MCP-1(4-76) and MCP-1(5-76) are active on both cells, whereas MCP-1(6-76), MCP-1(7-76), MCP-1(8-76), MCP-1(9-76), MCP-1(10-76) are inactive.

A glycosylated natural form of MCP-1/JE of 30 kDa has been found to be secreted into the conditioned medium by a medullary-type murine thymic epithelial cell line (MTEC1). The 30 kDa glycosylated form of MCP-1 shows lower specific chemotactic activity for both lymphocytes and monocytes than the 6-7 kDa unglycosylated form of MCP-1.

MCP-1 is expressed by monocytes, vascular endothelial cells, smooth muscle cells, glomerular mesangial cell, osteoblastic cells, and human pulmonary type 2 like epithelial cells in culture. It is constitutively produced by the human glioma U-105MG cell line. MCP-1 mRNA is induced in human peripheral blood mononuclear leukocytes by phytohemagglutinin (PHA), bacterial lipopolysaccharides, and IL1, but not by IL2, TNF, or IFN-gamma. In mesangial cells the synthesis and release of MCP-1 is rapidly induced by IgG complexes, but not monomeric IgG or F(ab')2 fragments of IgG.

MCP-1 is chemotactic for monocytes but not neutrophils. Maximal induction of migration is observed at a concentration of 10 ng/mL (see also: Chemotaxis). Point mutations have been described at two amino acid positions, which alter the factor so that it is then also chemotactic for neutrophils.

Elevated levels of MCP-1 are observed in atherosclerotic plaques that are rich in macrophages. The factor activates the tumoricidal activity of monocytes and macrophages in vivo. It regulates the expression of cell surface antigens (CD11c, CD11b) and the expression of cytokines (IL1, IL6). MCP-1 is a potent activator of human basophils, inducing degranulation and the release of histamines. In basophils activated by IL3, IL5 or GM-CSF MCP-1 enhances the synthesis of leukotriene C4.

IL1, TNF-alpha, PDGF, TGF-beta, and LIF induce the synthesis of MCP-1 in human articular chondrocytes, which may thus play an active role in the initiation and progression of degenerative and inflammatory arthropathies by promoting influx and cell activation of monocytes in synovial joints (see also: inflammation).

MCP-1 has been shown to exhibit biological activities other than Chemotaxis. It can induce the proliferation and activation of killer cells known as CHAK (CC-Chemokine-activated killer), which are similar to cells activated by IL2 (see also: LAK cells).

Two MCP-1-specific receptors have been cloned which signal in response to nanomolar concentrations of MCP-1. The two receptors differ in their carboxyl tails as a result of alternative splicing. They are related closely to the receptor for the Chemokines MIP-1-alpha and RANTES. MCP-1 also binds to a receptor designated D6. MCP-1 also binds to CCR10. MCP-1 has been shown to bind to the virus-encoded viroceptor M3. See also: S19 ribosomal protein.

The orphan receptor L-CCR has been suggested to function as an MCP-1 receptor in glial cells.


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(-2-) see: microbicidal cationic protein-1


Copyright 2012 by H IBELGAUFTS. All rights reserved.
ENTRY COMPLETED.


_____________________________________________________________________________

(-3-) see: macrophage cationic peptide-1


Copyright 2012 by H IBELGAUFTS. All rights reserved.
ENTRY COMPLETED.



 

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