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Gene Review:

CCL2 - chemokine (C-C motif) ligand 2

Macaca mulatta

Hendricks, E.E. et al., Mankowski, J.L. et al., Buch, S. et al., Henry, S.P. et al., Fox, H.S. et al., et al.

Henry, Beattie, Yeh, Chappel, Giclas, Mortari, Jagels, Kornbrust, Levin, Mankowski, Queen, Clements, Zink, Fox, Weed, Huitron-Resendiz, Baig, Horn, Dailey, Bischofberger, Henriksen, Buch, Sui, Potula, Pinson, Adany, Li, Huang, Li, Dhillon, Major, Narayan,

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Disease relevance of MCP-1

An acute increase in the level of the chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak of acute viremia, likely contributing to an early influx of immune cells into the CNS [1].
The studies showed that the higher susceptibility of rhesus macaques to X4 virus-mediated encephalitis correlated with heightened production of virus and MCP-1 in cultured macrophages from this species and that these effects were further enhanced with treatment with IL-4 [2].
We investigated the potential role of monocyte chemotactic protein-1 (MCP-1) in the pathogenesis of disseminated MAC, using the simian immunodeficiency virus (SIV)/macaque model of AIDS [3].
Animals that developed moderate to severe SIV encephalitis had significantly elevated levels of CSF IL-6, MCP-1, and SIV RNA during asymptomatic infection and persisting through terminal disease as compared to animals developing mild or no CNS disease [4].
Using the macaque model of the disease, the authors show here that X4, macrophage-tropic simian human immunodeficiency virus (SHIV) required the enhancing effect of interleukin (IL)-4 to achieve equivalent concentrations of virus and MCP-1 that are produced in macrophages infected with R5 viruses alone [5].

Psychiatry related information on MCP-1

Monkeys also experienced marked changes in bloodpressure (hypertension and hypotension), clinical signs of toxicity (lethargy and periorbital edema), fluctuations in circulating neutrophil counts, and elevations in serum cytokine levels (45-, 12-, and 4-fold increases in IL-6, MCP-1, and IL-12, respectively) [6].

High impact information on MCP-1

Primary infection with SIVmac239 was characterized by a higher level of IL-4, IL-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239 delta nef [7].
After challenge with M. avium, marked increases in serum MCP-1 levels were detected in SIV-infected macaques, a finding that was duplicated in coinoculated bronchoalveolar macrophages [3].
MCP-1 levels were significantly higher in SIV-infected macaques than in non-SIV-infected controls (327.1 vs. 151.5 pg/mL, respectively; P=.04), suggesting that up-regulation of MCP-1 contributes to the development of progressive mycobacterial disease [3].

Anatomical context of MCP-1

In this study, expression of IL-6, MCP-1, and viral RNA in cerebrospinal fluid collected from SIV-inoculated macaques during acute, asymptomatic, and terminal stages of infection was quantitated to determine whether one or several of these parameters paralleled the severity of SIV encephalitis [4].

Analytical, diagnostic and therapeutic context of MCP-1

Confocal microscopy showed that macrophages in the encephalitic brains were the major producers of MCP-1 [5].

References

Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys. Fox, H.S., Weed, M.R., Huitron-Resendiz, S., Baig, J., Horn, T.F., Dailey, P.J., Bischofberger, N., Henriksen, S.J. J. Clin. Invest. (2000) [Pubmed]
Neuropathogenesis of lentiviral infection in macaques: roles of CXCR4 and CCR5 viruses and interleukin-4 in enhancing monocyte chemoattractant protein-1 production in macrophages. Hicks, A., Potula, R., Sui, Y.J., Villinger, F., Pinson, D., Adany, I., Li, Z., Long, C., Cheney, P., Marcario, J., Novembre, F., Mueller, N., Kumar, A., Major, E., Narayan, O., Buch, S. Am. J. Pathol. (2002) [Pubmed]
Alterations in expression of monocyte chemotactic protein-1 in the simian immunodeficiency virus model of disseminated Mycobacterium avium complex. Hendricks, E.E., Lin, K.C., Boisvert, K., Pauley, D., Mansfield, K.G. J. Infect. Dis. (2004) [Pubmed]
Cerebrospinal fluid markers that predict SIV CNS disease. Mankowski, J.L., Queen, S.E., Clements, J.E., Zink, M.C. J. Neuroimmunol. (2004) [Pubmed]
Role of interleukin-4 and monocyte chemoattractant protein-1 in the neuropathogenesis of X4 simian human immunodeficiency virus infection in macaques. Buch, S., Sui, Y., Potula, R., Pinson, D., Adany, I., Li, Z., Huang, M., Li, S., Dhillon, N., Major, E., Narayan, O. J. Neurovirol. (2004) [Pubmed]
Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide. Henry, S.P., Beattie, G., Yeh, G., Chappel, A., Giclas, P., Mortari, A., Jagels, M.A., Kornbrust, D.J., Levin, A.A. Int. Immunopharmacol. (2002) [Pubmed]
Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy. Zou, W., Lackner, A.A., Simon, M., Durand-Gasselin, I., Galanaud, P., Desrosiers, R.C., Emilie, D. J. Virol. (1997) [Pubmed]

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CCL2	Bos taurus
CCL2	Canis lupus familiaris
CCL2	Homo sapiens
Ccl12	Mus musculus
CCL2	Pan troglodytes
Ccl12	Rattus norvegicus

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