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.
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.
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 ApoEhaplotype (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).
^ abEl Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (April 2007). "Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease". Nature Medicine. 13 (4): 432–8. doi:10.1038/nm1555. PMID17351623.
^Philipson O, Lord A, Gumucio A, O'Callaghan P, Lannfelt L, Nilsson LN (March 2010). "Animal models of amyloid-beta-related pathologies in Alzheimer's disease". The FEBS Journal. 277 (6): 1389–409. doi:10.1111/j.1742-4658.2010.07564.x. PMID20136653.
^Gorelick PB (October 2010). "Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials". Annals of the New York Academy of Sciences. 1207: 155–62. doi:10.1111/j.1749-6632.2010.05726.x. PMID20955439.
Sozzani S, Introna M, Bernasconi S, Polentarutti N, Cinque P, Poli G, Sica A, Mantovani A (July 1997). "MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression". Journal of Leukocyte Biology. 62 (1): 30–3. doi:10.1002/jlb.62.1.30. PMID9225989.
Choe H, Martin KA, Farzan M, Sodroski J, Gerard NP, Gerard C (June 1998). "Structural interactions between chemokine receptors, gp120 Env and CD4". Seminars in Immunology. 10 (3): 249–57. doi:10.1006/smim.1998.0127. PMID9653051.
Cunningham AL, Li S, Juarez J, Lynch G, Alali M, Naif H (September 2000). "The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes". Journal of Leukocyte Biology. 68 (3): 311–7. PMID10985245.
Ruibal-Ares BH, Belmonte L, Baré PC, Parodi CM, Massud I, de Bracco MM (January 2004). "HIV-1 infection and chemokine receptor modulation". Current HIV Research. 2 (1): 39–50. doi:10.2174/1570162043484997. PMID15053339.
Yamagami S, Tokuda Y, Ishii K, Tanaka H, Endo N (July 1994). "cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor". Biochemical and Biophysical Research Communications. 202 (2): 1156–62. doi:10.1006/bbrc.1994.2049. PMID8048929.
Samson M, Soularue P, Vassart G, Parmentier M (September 1996). "The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3". Genomics. 36 (3): 522–6. doi:10.1006/geno.1996.0498. PMID8884276.
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. PMID9058802.
Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA, Goedert JJ, O'Brien TR, Jacobson LP, Kaslow R, Buchbinder S, Vittinghoff E, Vlahov D, Hoots K, Hilgartner MW, O'Brien SJ (August 1997). "Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study". Science. 277 (5328): 959–65. doi:10.1126/science.277.5328.959. PMID9252328.
Frade JM, Mellado M, del Real G, Gutierrez-Ramos JC, Lind P, Martinez-A C (December 1997). "Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells". Journal of Immunology. 159 (11): 5576–84. PMID9548499.
Mummidi S, Ahuja SS, Gonzalez E, Anderson SA, Santiago EN, Stephan KT, Craig FE, O'Connell P, Tryon V, Clark RA, Dolan MJ, Ahuja SK (July 1998). "Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression". Nature Medicine. 4 (7): 786–93. doi:10.1038/nm0798-786. PMID9662369.