This gene encodes two isoforms of a receptor formonocyte chemoattractant protein-1 (CCL2), achemokine which specifically mediatesmonocytechemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such asrheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependentcalcium mobilization and inhibition ofadenylyl cyclase.[5]
Within the fat (adipose) tissue of CCR2 deficientmice, there is an increased number ofeosinophils, greater alternativemacrophage activation, and a propensity towards type 2cytokine expression. Furthermore, this effect was exaggerated when the mice becameobese from a high fat diet.[9]
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.[10] An excessive monocytes infiltration generates higher inflammation and increases the risk ofheart failure.
In anobservational study ofgene expression in bloodleukocytes in humans, Harrieset al. found evidence of arelationship between expression ofCCR2 and cognitive function (assessed using themini-mental state examination, MMSE).[11] HigherCCR2 expression was associated with worse performance on the MMSE assessment of cognitive function. The same study found thatCCR2 expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory relatedtranscripts only. Harrieset al. suggest thatCCR2 signaling may have a direct role in human cognition, partly because expression ofCCR2 was associated with theApoEhaplotype (previously associated with Alzheimer's disease), but also becauseCCL2 is expressed at high concentrations inmacrophages found inatherosclerotic plaques and in brainmicroglia.[6] The difference in observations between mice (CCR2 depletion causes cognitive decline) and humans (higherCCR2 associated with lower cognitive function) could be due to increaseddemand for macrophage activation during cognitive decline, associated with increasedβ-amyloid deposition (a core feature of Alzheimer's disease progression).
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Polentarutti N, Allavena P, Bianchi G, Giardina G, Basile A, Sozzani S, Mantovani A, Introna M (March 1997). "IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences".Journal of Immunology.158 (6):2689–94.doi:10.4049/jimmunol.158.6.2689.PMID9058802.S2CID24232430.
Daugherty BL, Springer MS (April 1997). "The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3) cluster within 285 kb on human chromosome 3p21".Genomics.41 (2):294–5.doi:10.1006/geno.1997.4626.PMID9143512.
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