CCR2

C-C chemokine receptor type 2 (CCR2 or CD192 (cluster of differentiation 192) is a protein that in humans is encoded by the "CCR2" gene. CCR2 is a CC chemokine receptor.
Gene.
This CCR2 gene is located in the chemokine receptor gene cluster region. Two alternatively spliced transcript variants are expressed by the gene.
Function.
This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1 (CCL2), a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of adenylyl cyclase.
Animal studies.
Alzheimer.
"CCR2" deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to wild type mice. This is not the first time that immune function and inflammation have been linked to age-related cognitive decline (i.e. dementia).
Obesity.
Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative macrophage activation, and a propensity towards type 2 cytokine expression. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet.
Myocardial Infarct.
CCR2 surface expression on blood monocytes changes in a time-of-day–dependent manner (being higher at the beginning of the active phase) and affects monocytes recruitment in tissues including the heart. As a consequence when an acute ischemic event happens during the active phase, monocytes are more susceptible to invade the heart. An excessive monocytes infiltration generates higher inflammation and increases the risk of heart failure.
Clinical significance.
In an observational study of gene expression in blood leukocytes in humans, Harries "et al." found evidence of a relationship between expression of "CCR2" and cognitive function (assessed using the mini-mental state examination, MMSE). Higher "CCR2" expression was associated with worse performance on the MMSE assessment of cognitive function. The same study found that "CCR2" expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory related transcripts only. Harries "et al." suggest that "CCR2" signaling may have a direct role in human cognition, partly because expression of "CCR2" was associated with the ApoE haplotype (previously associated with Alzheimer's disease), but also because "CCL2" is expressed at high concentrations in macrophages found in atherosclerotic plaques and in brain microglia. The difference in observations between mice ("CCR2" depletion causes cognitive decline) and humans (higher "CCR2" associated with lower cognitive function) could be due to increased "demand" for macrophage activation during cognitive decline, associated with increased β-amyloid deposition (a core feature of Alzheimer's disease progression).