Monocyte Chemotactic Protein-2 (MCP-2) Uses CCR1 AND CCR2B as Its Functional Receptors

Gong, Xiaoqi; Gong, Wanghua; Kuhns, Douglas B.; Ben‐Baruch, Adit; Howard, O. M. Zack; Wang, Ji Ming

doi:10.1074/jbc.272.18.11682

Cited by 124 publications

(85 citation statements)

References 29 publications

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“…C5a (through the C5aR receptor) and CXCL5/CXCL2 (through the CXCR2 receptor) are primarily chemoattractants for neutrophils, 22,23 although they are also involved in T-cell migration to the intestinal mucosa 24 and to the brain, 25,26 whereas CCL5 and CCL8 can attract monocytes, NK cells, and activated T cells (through CCR5 and CCR1 receptors). [27][28][29] However, our data show a lower or similar percentage of C5aR-, CXCR2-, CCR1-, and CCR5-expressing CD8 T cells in the bladder with or without IVES Ty21a immunostimulation, suggesting an indirect effect of the cognate chemokines on the preferential increase in CD8 T cells in the bladder.…”

Section: Discussioncontrasting

confidence: 47%

LocalSalmonellaimmunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor

et al. 2015

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The efficacy of antitumoral responses can be increased using combinatorial vaccine strategies. We recently showed that vaccination could be optimized by local administration of diverse molecular or bacterial agents to target and augment antitumoral CD8 T cells in the genital mucosa (GM) and increase regression of cervical cancer in an animal model. Non muscle-invasive bladder cancer is another disease that is easily amenable to local therapies. In contrast to data obtained in the GM, in this study we show that intravesical (IVES) instillation of synthetic toll-like receptor (TLR) agonists only modestly induced recruitment of CD8 T cells to the bladder. However, IVES administration of Ty21a, a live bacterial vaccine against typhoid fever, was much more effective and increased the number of total and vaccinespecific CD8 T cells in the bladder approximately 10 fold. Comparison of chemokines induced in the bladder by either CpG (a TLR-9 agonist) or Ty21a highlighted the preferential increase in complement component 5a, CXCL5, CXCL2, CCL8, and CCL5 by Ty21a, suggesting their involvement in the attraction of T cells to the bladder. IVES treatment with Ty21a after vaccination also significantly increased tumor regression compared to vaccination alone, resulting in 90% survival in an orthotopic murine model of bladder cancer expressing a prototype tumor antigen. Our data demonstrate that combining vaccination with local immunostimulation may be an effective treatment strategy for different types of cancer and also highlight the great potential of the Ty21a vaccine, which is routinely used worldwide, in such combinatorial therapies.

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Section: Discussioncontrasting

confidence: 47%

LocalSalmonellaimmunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor

et al. 2015

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“…Since deletion of CCR2 did not affect virus levels in the brain, it is probable that the effect of CCR2 on Fr98-mediated neurological disease was due to chemokine binding and signaling through CCR2. CCR2 binds several chemokines, primarily MCP-1, MCP-2, MCP-3, and MCP-5 (3,11,30). We were therefore interested in determining if the expression of these genes was upregulated by Fr98 infection and if any of these genes were upregulated prior to disease onset.…”

Section: Resultsmentioning

confidence: 99%

MCP-1 and CCR2 Contribute to Non-Lymphocyte-Mediated Brain Disease Induced by Fr98 Polytropic Retrovirus Infection in Mice: Role for Astrocytes in Retroviral Neuropathogenesis

Peterson

Errett

Wei

et al. 2004

J Virol

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Virus infection of the central nervous system (CNS) often results in chemokine upregulation. Although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated CNS disease. In these instances, the effect of chemokine upregulation on neurological disease is unclear. In vitro, several chemokines including monocyte chemotactic protein 1 (MCP-1) protect neurons from apoptosis. Therefore, in vivo, chemokine upregulation may be a protective host response to CNS damage. Alternatively, chemokines may contribute to pathogenesis by stimulating intrinsic brain cells or recruiting macrophages to the brain. To investigate these possibilities, we studied a neurovirulent retrovirus, Fr98, that induces severe non-lymphocyte-mediated neurological disease and causes the upregulation of several chemokines that bind to chemokine receptors CCR2 and CCR5. Knockout mice deficient in CCR2 had reduced susceptibility to Fr98 pathogenesis, with significantly fewer mice developing clinical disease than did wild-type controls. In contrast, no reduction in Fr98-induced disease was observed in CCR5 knockout mice. Thus, signaling through CCR2, but not CCR5, plays an important role in Fr98-mediated pathogenesis. Three ligands for CCR2 (MCP-1, MCP-3, and MCP-5) were upregulated during Fr98 infection of the brain. Antibodyblocking experiments demonstrated that MCP-1 was important for retrovirus-induced neurological disease. In situ hybridization analysis revealed that MCP-1 was expressed by glial fibrillary acidic protein-positive astrocytes. Thus, astrocytes, previously not thought to play an effector role in the disease process were found to contribute to pathogenesis through the production of MCP-1. This study also demonstrates that chemokines can mediate pathogenesis in the CNS in the absence of lymphocytic infiltrate and gives credence to the hypothesis that chemokine upregulation is a mechanism by which retroviruses such as human immunodeficiency virus induce neurological damage.

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“…Expression of CCR2 is inhibited in monocytes and T cells by LPS and IFN-␥ (35,36) and up-regulated by IL-2, IL-4, IL-10, and IL-12 in T cells (35). Although MCP-1 is the principal ligand for CCR2, other ligands include MCP-2, MCP-3, MCP-4, MCP-5, and HIV Tat (37)(38)(39)(40)(41). However, in mice, only MCP-1, MCP-3, and MCP-5 bind CCR2.…”

Section: Ccr2 ϫ/ϫ Mice Are Protected From Pulmonary Fibrosismentioning

confidence: 99%

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

Moore

Paine

Christensen

et al. 2001

The Journal of Immunology

337

292

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Pulmonary fibrosis can be modeled in animals by intratracheal instillation of FITC, which results in acute lung injury, inflammation, and extracellular matrix deposition. We have previously shown that despite chronic inflammation, this model of pulmonary fibrosis is lymphocyte independent. The CC chemokine monocyte-chemoattractant protein-1 is induced following FITC deposition. Therefore, we have investigated the contribution of the main monocyte-chemoattractant protein-1 chemokine receptor, CCR2, to the fibrotic disease process. We demonstrate that CCR2−/− mice are protected from fibrosis in both the FITC and bleomycin pulmonary fibrosis models. The protection is specific for the absence of CCR2, as CCR5−/− mice are not protected. The protection is not explained by differences in acute lung injury, or the magnitude or composition of inflammatory cells. FITC-treated CCR2−/− mice display differential patterns of cellular activation as evidenced by the altered production of cytokines and growth factors following FITC inoculation compared with wild-type controls. CCR2−/− mice have increased levels of GM-CSF and reduced levels of TNF-α compared with FITC-treated CCR2+/+ mice. Thus, CCR2 signaling promotes a profibrotic cytokine cascade following FITC administration.

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Monocyte Chemotactic Protein-2 (MCP-2) Uses CCR1 AND CCR2B as Its Functional Receptors

Abstract: Monocyte chemotactic protein (MCP)-

Cited by 124 publications

References 29 publications

LocalSalmonellaimmunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor

LocalSalmonellaimmunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor

MCP-1 and CCR2 Contribute to Non-Lymphocyte-Mediated Brain Disease Induced by Fr98 Polytropic Retrovirus Infection in Mice: Role for Astrocytes in Retroviral Neuropathogenesis

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

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