LPS down-regulates the expression of chemokine receptor CCR2 in mice and abolishes macrophage infiltration in acute inflammation

Zhou, Yuhong; Yang, Yi Yuan; Warr, Glenn A.; Bravo, Rodrigo

doi:10.1002/jlb.65.2.265

Cited by 46 publications

(31 citation statements)

References 29 publications

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“…It is well established that LPS activates phagocytic leukocytes, including microglia, to release proinflammatory mediators. Furthermore, although LPS rapidly increases gene transcription and protein production of a number of cytokines and chemokines, it down-regulates the expression and function of several chemokine receptors, including CCR1, CCR2, and CCR5 (27)(28)(29)(30) in monocytes or CXCR1 and CXCR2 in neutrophils (31)(32)(33)(34). This reciprocal upregulation of the expression of ligands vs down-regulation of receptors by LPS has been proposed as a protective host reaction aimed at limiting excessive inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Bacterial Lipopolysaccharide Selectively Up-Regulates the Function of the Chemotactic Peptide Receptor Formyl Peptide Receptor 2 in Murine Microglial Cells

Cui

Gong

et al. 2002

The Journal of Immunology

110

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Receptors for the bacterial chemotactic peptide fMLP are implicated in inflammation and host defense against microbial infection. We investigated the expression and function of fMLPR in microglial cells, which share characteristics of mononuclear phagocytes and play an important role in proinflammatory responses in the CNS. The expression of the genes encoding formyl peptide receptor (FPR)1 and FPR2, the high- and low-affinity fMLPR, was detected in a murine microglial cell line N9, but these cells did not respond to chemotactic agonists known for these receptors. N9 cells incubated with bacterial LPS increased the expression of fMLPR genes and developed a species of specific, but low-affinity, binding sites for fMLP, in association with marked calcium mobilization and chemotaxis responses to fMLP in a concentration range that typically activated the low-affinity receptor FPR2. In addition, LPS-treated N9 cells were chemoattracted by two FPR2-specific agonists, the HIV-1 envelope-derived V3 peptide, and the 42 aa form of the amyloid β peptide which is a pathogenic agent in Alzheimer’s disease. Primary murine microglial cells also expressed FPR1 and FPR2 genes, but similar to N9 cells, exhibited FPR2-mediated activation only after LPS treatment. In contrast to its effect on the function of FPR2, LPS reduced N9 cell binding and biological responses to the chemokine stromal cell-derived factor-1α. Thus, LPS selectively modulates the function of chemoattractant receptors in microglia and may promote host response in inflammatory diseases in the CNS.

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Section: Discussionmentioning

confidence: 99%

Bacterial Lipopolysaccharide Selectively Up-Regulates the Function of the Chemotactic Peptide Receptor Formyl Peptide Receptor 2 in Murine Microglial Cells

Cui

Gong

et al. 2002

The Journal of Immunology

110

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“…It has been shown that exposure to high concentrations of plasma LDL results in an upregulation of CCR2 expression and enhanced monocyte chemotaxis [26], while HDL downregulates CCR2 expression [27]. Exposure of monocytes to oxidised LDL, inflammatory cytokines, LPS and MCP-1 itself [26, 28, 29]has been shown to downregulate CCR2 expression on monocytes. CCR2 is decreased during monocyte differentiation [30]and oxLDL is able to stimulate differentiation [26].…”

Section: Discussionmentioning

confidence: 99%

Localisation of mRNA for JE/MCP-1 and Its Receptor CCR2 in Atherosclerotic Lesions of the ApoE Knockout Mouse

et al. 2000

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MCP-1 has potent chemotactic activity for monocytes and is strongly implicated in the pathogenesis of atherosclerosis. In the present study, we have used in situ hybridisation to examine the gene expression of JE, the murine homologue of MCP-1, and its receptor, CCR2, during the development of atherosclerotic lesions in the ApoE knockout mouse. Interestingly, the earliest expression of JE detected during lesion development was found to be localised in mesenchymal cells in the adventitia and not in the intima. Macrophages were subsequently found to accumulate in these affected regions of the adventitia and these cells were found to express high levels of JE. At this stage, early macrophage-rich lesions with high expression of JE were also seen in the intima, but expression of mRNA for the receptor for JE (CCR2) was only found on adventitial macrophages and not in the intima. This sequence of events suggests that adventitial inflammation may be an important early event in lesion development and responsible for the subsequent accumulation of macrophages in the intima possibly by recruitment from the adventitia as well as via the vessel lumen.

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“…high monocytes in the infected and noninfected bladder and also in the blood CCR2 has been proposed to mediate recruitment of monocytes to sites of infection (14,15,17,18). Since Gr1 high monocytes have been shown to express more CCR2 (1), we investigated whether their preferential recruitment to the infected bladder (Fig.…”

Section: Ccr2 Deficiency Reduces Gr1mentioning

confidence: 99%

“…CCR2 is required for monocyte recruitment into inflamed or infected tissue, as evidenced by a major reduction of infiltrating monocytes in CCR2 Ϫ/Ϫ mice (14 -16) and aggravated infection (17,18). This has been particularly well studied in infection with Listeria monocytogenes, a Gram-positive rod that targets the spleen (15,(17)(18)(19). Likewise, inflammatory diseases involving aberrant monocyte recruitment were attenuated in CCR2 Ϫ/Ϫ mice (20 -22).…”

mentioning

confidence: 99%

CCR2 Mediates Homeostatic and Inflammatory Release of Gr1high Monocytes from the Bone Marrow, but Is Dispensable for Bladder Infiltration in Bacterial Urinary Tract Infection

Engel

Maurer

Tittel

et al. 2008

The Journal of Immunology

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CCR2 is thought to recruit monocytes to sites of infection. Two subpopulations of murine blood monocytes differing in Gr1 and CCR2 expression have been described. The exact role of CCR2 in migration of CCR2lowGr1low and CCR2highGr1high monocytes into nonlymphoid tissue is controversial. In this study, we have addressed this question in a murine model of bacterial urinary tract infection. Only Gr1high monocytes were recruited into the infected bladder. CCR2 deficiency reduced their frequency in this organ, indicating a requirement of this chemokine receptor. Importantly, CCR2-deficient mice also showed reduced Gr1high monocyte numbers in the blood, but not in the bone marrow (BM), indicating that CCR2 acted at the step of monocyte release into the circulation. The same was found also in noninfected mice, indicating a further involvement of CCR2 in steady-state BM egress. An additional requirement of CCR2 in monocyte recruitment from the blood into the bladder was excluded by tracking particle-labeled endogenous monocytes and by adoptive transfer of BM-derived monocyte subsets. These findings demonstrate that CCR2 governs homeostatic and infection-triggered release of Gr1high monocytes from the BM into the blood but is dispensable for recruitment into a nonlymphoid tissue.

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LPS down-regulates the expression of chemokine receptor CCR2 in mice and abolishes macrophage infiltration in acute inflammation

Cited by 46 publications

References 29 publications

Bacterial Lipopolysaccharide Selectively Up-Regulates the Function of the Chemotactic Peptide Receptor Formyl Peptide Receptor 2 in Murine Microglial Cells

Bacterial Lipopolysaccharide Selectively Up-Regulates the Function of the Chemotactic Peptide Receptor Formyl Peptide Receptor 2 in Murine Microglial Cells

Localisation of mRNA for JE/MCP-1 and Its Receptor CCR2 in Atherosclerotic Lesions of the ApoE Knockout Mouse

CCR2 Mediates Homeostatic and Inflammatory Release of Gr1high Monocytes from the Bone Marrow, but Is Dispensable for Bladder Infiltration in Bacterial Urinary Tract Infection

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