Monocyte chemotactic protein-1 gene and protein expression in atherogenesis of hypercholesterolemic rabbits

Chen, Yuh‐Lien; Chang, Ya Ju; Jiang, Meei Jyh

doi:10.1016/s0021-9150(98)00285-8

Cited by 51 publications

(28 citation statements)

References 30 publications

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“…It has been reported to be involved in many diseases, including asthma (49,50), rheumatoid arthritis (51,52), and atherosclerosis (53,54). In addition, MCP1 plays a very important role in excitotoxic injury.…”

Section: Discussionmentioning

confidence: 99%

The C Terminus of Mouse Monocyte Chemoattractant Protein 1 (MCP1) Mediates MCP1 Dimerization while Blocking Its Chemotactic Potency

Yao

Tsirka

2010

Journal of Biological Chemistry

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The extracellular protease plasmin cleaves mouse MCP1 (monocyte chemoattractant protein 1) at lysine 104, releasing a 50-amino acid C-terminal domain. The cleavage event increases the chemotactic activity of MCP1 and, by doing so, promotes the progression of excitotoxic injury in the central nervous system in pathological settings. The mechanism through which the cleavage event enhances MCP1-mediated chemoattraction is unknown; to investigate it, we use wild-type and mutant forms of recombinant MCP1. Full-length MCP1 (FL-MCP1) is secreted by cells as a dimer or multimer. We show that a mutant truncated at the C terminus, K104Stop-MCP1, does not dimerize, revealing that the C terminus mediates the interaction. Microglia, the immune-like cells normally present in the brain, derive from the bone marrow (1-5), enter the central nervous system (CNS) early during development, and reside in the parenchyma in a resting state characterized by ramified morphology. In the healthy brain, they continually extend and retract their processes to sense changes in the surrounding microenvironment (6). However, when there is an injury in the CNS, microglia switch to an activated state characterized by changes in gene expression, morphology, and proliferation (6 -16). The activated microglia then migrate to the site of injury and modify the injury outcome.The migration of microglia to the site of injury is stimulated by the local release of chemokines, a superfamily of structurally related small proteins that function as chemoattractants. A potent chemoattractant for monocytes/microglia (17), MCP1 (monocyte chemoattractant protein-1; also called CCL2), is upregulated in many types of CNS injury, including ischemia, hemorrhage, trauma, infection, hypoxia, and peripheral nerve axotomy (18 -24). The MCP1 protein is highly conserved in the N terminus among different species, whereas the C terminus is much more variable. The rodent MCP1 C terminus is decorated extensively with O-linked carbohydrates (25), which bind both soluble glycosaminoglycans (GAGs) and GAGs immobilized on the cell surface. Soluble GAGs inhibit the binding of MCP1 to its high affinity receptor CCR2 (30), which is expressed by microglia, astrocytes, and microvascular endothelial cells in the brain (26,27). Cell surface GAGs, on the other hand, have been reported to concentrate MCP1 locally, promote MCP1 oligomerization, and thus facilitate the binding of MCP1 to CCR2 (28 -31). Whether MCP1 functions as a monomer or homodimer, however, is still under debate. Although it is believed that MCP1 exerts its function as a homodimer (25,32), it has also been suggested that MCP1 can bind to CCR2 and induce downstream signaling as a monomer (33,34). It should be noted, however, that these experiments were conducted using human MCP1, not rodent MCP1, which contains a heavily glycosylated C-terminal extension.Previous studies in our laboratory have shown that 1) the highly glycosylated C-terminal extension of mouse MCP1 is removed by plasmin, the active protease of plasminogen,...

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Section: Discussionmentioning

confidence: 99%

The C Terminus of Mouse Monocyte Chemoattractant Protein 1 (MCP1) Mediates MCP1 Dimerization while Blocking Its Chemotactic Potency

Yao

Tsirka

2010

Journal of Biological Chemistry

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“…In addition, the expression of VCAM-1 preceding the infiltration of the subendothelial space by macrophages has been studied [128], as have the proteins, including MCP-1. In hypercholesterolaemic rabbits, this protein is over-expressed when the serum-cholesterol levels rise in macrophages and smooth-muscle cells, contributing to the development of fatty streaks [2].…”

Section: Rabbitsmentioning

confidence: 99%

“…The rise of the plasma-cholesterol levels is known to be accompanied by an overexpression of monocytic chemotactic protein-1 (MCP-1) by the macrophages and vascular smoothmuscle cells, which play a pivotal role in the development of fatty streaks [2]. In this way, an endothelium altered by hypercholesterolaemia leads to a pre-thrombosis state that begins with the aggregation of platelets.…”

Section: Introductionmentioning

confidence: 99%

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sebastián¹,

Corral²,

Montañana³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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“…They are proinflammatory in nature, and chemotactic for monocytes, eosinophils, and basophils. Chemokine expression is increased in a number of different pathologic processes, including synovial pannus of rheumatoid joints, autoimmune lesions of multiple sclerosis, affected mucosal surfaces in ulcerative colitis and Crohn's disease, lung inflammation in chronic bronchitis, sarcoidosis, and asthma, and the vascular inflammation that characterizes atherosclerosis (8)(9)(10)(11)(12). Overexpression of MCP-1 by SSc fibroblasts was first found to underlie the promotion of leukocyte migration across endothelial cell monolayers by these cells (13), and other studies have subsequently confirmed overexpression of MCP-1 in SSc tissues (14,15) and by lesional fibroblasts in culture (16).…”

Section: Mcp-3 In Transgenic Mice and By Transient Transfection Assaymentioning

confidence: 99%

Monocyte chemoattractant protein 3 as a mediator of fibrosis: Overexpression in systemic sclerosis and the type 1 tight‐skin mouse

Ong¹,

Evans²,

Xu³

et al. 2003

Arthritis & Rheumatism

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Monocyte chemotactic protein-1 gene and protein expression in atherogenesis of hypercholesterolemic rabbits

Cited by 51 publications

References 30 publications

The C Terminus of Mouse Monocyte Chemoattractant Protein 1 (MCP1) Mediates MCP1 Dimerization while Blocking Its Chemotactic Potency

The C Terminus of Mouse Monocyte Chemoattractant Protein 1 (MCP1) Mediates MCP1 Dimerization while Blocking Its Chemotactic Potency

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Monocyte chemoattractant protein 3 as a mediator of fibrosis: Overexpression in systemic sclerosis and the type 1 tight‐skin mouse

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