Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: Therapeutic opportunities and controversies

被引:205
作者
Daly, C
Rollins, BJ
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Med Oncol, Boston, MA USA
关键词
chemokine; inflammation; T helper cell; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NEUTROPHIL-ACTIVATING PROPERTIES; MULTIPLE-SCLEROSIS LESIONS; HISTAMINE-RELEASING FACTOR; CHEMOKINE RECEPTOR (CCR)2; CORONARY-ARTERY DISEASE; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; KNOCKOUT MICE; NEOINTIMAL HYPERPLASIA;
D O I
10.1038/sj.mn.7800190
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2(-/-) and CCR2(-/-) mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease.
引用
收藏
页码:247 / 257
页数:11
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