CCR2 Signaling Contributes to Ischemia-Reperfusion Injury in Kidney

Furuichi, Kengo; Wada, Takashi; Iwata, Yasunori; Kitagawa, Kiyoki; Kobayashi, Ken; Hashimoto, Hiroyuki; Ishiwata, Yoichi; Asano, Masahide; Wang, Hui; Matsushima, Kouji; Takeya, Motohiro; Kuziel, William A.; Mukaida, Naofumi; Yokoyama, Hitoshi

doi:10.1097/01.asn.0000089563.63641.a8

Cited by 223 publications

(183 citation statements)

References 52 publications

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“…33 The CC chemokine MCP-1 and CXC chemokine MIP-2 are also important mediators in the pathogenesis of AKI. 34 Upregulation of MCP-1 and MIP-2 leads to neutrophil recruitment during AKI induced by renal IR or nephrotoxic agents. 35 Indeed, our study showed that liver IR not only caused rapid infiltration of neutrophils into liver but also caused neutrophil infiltration in kidney.…”

Section: Discussionmentioning

confidence: 99%

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park

Chen

Kim

et al. 2010

Laboratory Investigation

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Section: Discussionmentioning

confidence: 99%

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park

Chen

Kim

et al. 2010

Laboratory Investigation

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“…For example, abrogation of CCR1 or CCR2 signaling in a mouse model of AKI results in reduction of interstitial macrophage infiltrates. 36,37 Delivery of a truncated MCP-1/CCL2 protein into mice with IRI also blocks activation of CCR2, thereby inhibiting macrophage infiltration. 38,39 Interestingly, injured kidneys from mice lacking CCR1 also reduce expression of CCR1 ligands(MIP-1␣/CCL3andRANTES/CCL5), suggestingtheexistenceofapositivefeedback loop for chemokine production.…”

Section: Role Of CCL and Cxc3l Families In Akimentioning

confidence: 99%

“…38,39 Interestingly, injured kidneys from mice lacking CCR1 also reduce expression of CCR1 ligands(MIP-1␣/CCL3andRANTES/CCL5), suggestingtheexistenceofapositivefeedback loop for chemokine production. 36,37 Several recent reports highlight the protective role of Tregs during IRI. 40 -43 However, the source of the renal Tregs in response to IRI is uncertain.…”

Section: Role Of CCL and Cxc3l Families In Akimentioning

confidence: 99%

“…As renal expression of MCP-1/CCL-2 is greatly elevated after IRI and CCR2 has been shown to guide Tregs toward arthritic joints, CCL chemokines may function to regulate Treg cell accumulation in acute kidney injury. 44,36,45 Dendritic cells (DCs) are also an important link between innate and adaptive immunity and their role in renal injury is well known. 46 After IRI, renal DCs produce both the proinflammatory cytokines (TNF-␣, IL-6, and CCL) and chemokines (MCP-1/ CCL2 and RANTES/CCL5).…”

Section: Role Of CCL and Cxc3l Families In Akimentioning

confidence: 99%

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Chemokines in Renal Injury

Chung

Lan

2011

Journal of the American Society of Nephrology

240

181

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Renal inflammation underlies many chronic kidney diseases and the infiltration of leukocytes mediates much of the nephritogenic inflammatory response. As several recent reviews have dealt with the basic biology, mouse models, and blockade studies of chemokines in renal diseases, [1][2][3][4][5][6][7][8][9][10][11] we focus here on recent developments in pathophysiology of that chemokine effect. CHEMOKINES AND CHEMOKINE RECEPTORSChemokines are a group of chemotactic cytokines (approximately 8 to 17 kD) with the ability to bind G-proteincoupled receptors and act as potent attractants for leukocytes in acute and chronic inflammation. There are four subfamilies of chemokines, including CCL, CXCL, CX3CL, and CL (Figure 1). 7,6 At present, 19 receptors are known ( Figure 1). 6,7 The large CC chemokine family has the first two cysteine residues adjacent to each other, whereas the CXC family has a single amino acid residue in between the first two cysteines. Fractalkine (CX3CL1) is the only member of the CX3C chemokine family where three amino acid residues separate the first two cysteines. Finally, two related chemokines absent the two cysteine residues that bind the XCR1 receptor belong to the XC family. As shown in Figure 1, many chemokines bind multiple receptors and most receptors bind multiple chemokines. However, CC chemokine receptors exclusively bind CC chemokines and CXC receptors bind only CXC chemokines.Chemokines and their corresponding receptors are expressed in different cell types (Figure 2). 7,12 Generally speaking, monocytes are mostly attracted by CCL chemokines acting through CCR1, CCR2, andCCR5receptors,whereasneutrophilsare the target of CXCL chemokines through REGULATION OF CHEMOKINE EXPRESSIONOn the basis of their regulation and production, chemokines can be classified broadly as homeostatic/lymphoid or inflammatory chemokines. The former is responsible for leukocyte homing and ABSTRACTThe main function of chemokines is to guide inflammatory cells in their migration to sites of inflammation. During the last 2 decades, an expanding number of chemokines and their receptors have driven broad inquiry into how inflammatory cells are recruited in a variety of diseases. Although this review focuses on chemokines and their receptors in renal injury, proinflammatory IL-17, TGF␤, and TWEAK signaling pathways also play a critical role in their expression. Recent studies in transgenic mice as well as blockade of chemokine signaling by neutralizing ligands or receptor antagonists now allow direct interrogation of chemokine action. The emerging role of regulatory T cells and Th17 cells during renal injury also forges tight relationships between chemokines and T cell infiltration in the development of kidney disease. As chemokine receptor blockade inches toward clinical use, the field remains an attractive area with potential for unexpected opportunity in the future.

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“…MCP-1 is an important chemokine associated with increased macrophage numbers in kidney diseases (17). Therefore, MCP-1 levels were measured in renal homogenates.…”

Section: Cytokine Treatment Leads To Increased Macrophage Influx Intomentioning

confidence: 99%

Hematopoietic Stem Cell Mobilization Therapy Accelerates Recovery of Renal Function Independent of Stem Cell Contribution

Stokman

Leemans

Claessen

et al. 2005

Journal of the American Society of Nephrology

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Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability of hematopoietic stem cells, induced by stem cell factor and granulocyte colony-stimulating factor, to the injured kidney provides an adequate strategy for stem cell-based therapy to counteract renal ischemia/reperfusion injury. It is interesting that cytokine treatment before injury resulted in significant enhancement of function recovery of the kidney. This, however, was not due to increased incorporation of tubular epithelial cells from bone marrow origin. Importantly, cytokine treatment resulted in impaired influx of granulocytes into the injured kidney. Although cytokine treatment improved renal function rapidly after ischemic injury, the results show that the underlying mechanism likely is not based on stem cell transdifferentiation but rather on altered inflammatory kinetics.J Am Soc Nephrol 16: 1684 -1692 , 2005 . doi: 10.1681 A cute renal failure is a major clinical problem that affects up to 5% of all hospitalized patients (1). The major cause is tubular necrosis as a consequence of ischemic injury after episodes of hypotension or surgical vascular clamping. Moreover, renal transplantation is always associated with some degree of ischemia/reperfusion (I/R) injury. The development of specific therapies for I/R injury has proved problematic; therefore, therapy remains largely supportive.Recent studies suggested the involvement of bone marrow (BM)-derived stem cells in the regeneration of nonhematopoietic tissues. BM-derived cells with an endothelial (2), epithelial (3,4), or mesangial (5) phenotype were detected in murine kidneys after injury. Case studies have described the presence of Y chromosome-containing tubular epithelial cells (TEC) in kidneys from female donors that were transplanted into male recipients (6,7). These observations have led to the hypothesis that aside from intrinsic cellular proliferation, BM-derived cells contribute to kidney healing or maintenance.Experimental studies have provided evidence for a limited contribution of BM-derived cells to the injured kidney, perhaps as a direct consequence of the low circulating levels of BMderived stem cells. A study by Orlic et al. (8) demonstrated that cytokine-induced mobilization of BM hematopoietic stem cells (HSC) before the induction of myocardial infarction increased heart function significantly. On the basis of the study by Orlic et al., we mobilized HSC with stem cell factor (SCF) combined with granulocyte colony-stimulating factor (G-CSF), which operate synergistically in inducing egress of HSC from the BM compared with G-CSF alone (9).Here we report that cytokine treatment before renal I/R in mice accelerates renal function recovery compared with controls. The underlying mechanism does not depend on a biologically significant contribu...

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CCR2 Signaling Contributes to Ischemia-Reperfusion Injury in Kidney

Cited by 223 publications

References 52 publications

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Chemokines in Renal Injury

Hematopoietic Stem Cell Mobilization Therapy Accelerates Recovery of Renal Function Independent of Stem Cell Contribution

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