C-C chemokine receptor type 2 (CCR2 or CD192 ( cluster of differentiation 192) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''CCR2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. CCR2 is a CC chemokine receptor.

Gene

This CCR2 gene is located in the chemokine receptor gene cluster region. Two

alternatively spliced Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may b ...

transcript variants are expressed by the gene.

Function

This gene encodes two isoforms of a receptor for

monocyte chemoattractant protein-1 ''For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.'' The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL ...

(CCL2), a

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additi ...

which specifically mediates

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

mobilization and inhibition of

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

Animal studies

Alzheimer

''CCR2'' deficient mice have been shown to develop an accelerated

Alzheimer's Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...

-like pathology in comparison to wild type mice. This is not the first time that

immune function The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splin ...

and

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

have been linked to age-related cognitive decline (i.e.

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

Obesity

Within the fat ( adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

activation, and a propensity towards type 2

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

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 Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

Clinical significance

In an observational study of

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. T ...

in blood

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mu ...

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 Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease. APOE belongs to a family of fat-binding proteins called apolipoproteins. ...

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA o ...

(previously associated with Alzheimer's disease), but also because ''CCL2'' is expressed at high concentrations in

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

found in

atherosclerotic plaques Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

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 Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...

deposition (a core feature of Alzheimer's disease progression).

References

External links

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Information Hyperlinked Over Proteins
{{Chemokine receptor modulators Chemokine receptors Clusters of differentiation