Role of CD11a and CD11b in ischemic acute renal failure in rats

Rabb, Hamid; Mendiola, Christina; Dietz, John R.; Saba, Sabiha R.; Issekutz, Thomas B.; Abanilla, F.; Bonventre, Joseph V.; Ramírez, Germán

doi:10.1152/ajprenal.1994.267.6.f1052

Cited by 95 publications

(95 citation statements)

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“…Although L-selectin has been shown to be important in I/R injury in different tissues, such as the liver (24), skeletal muscle (25), and heart muscle (26), its role in renal I/R injury is controversial (15). Integrins implicated in the inflammatory response to renal ischemia are the ␤2 integrins CD11a and CD11b (27,28), which are known to bind to intercellular adhesion molecule-1 on the endothelium. This binding may ultimately result in transmigration of the leukocyte across the endothelial monolayer and the underlying extracellular matrix into the renal interstitium.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Although it is well demonstrated that leukocyte adhesion molecule blockade plays a tissue protective role in IRI in muscle and heart, it is still a matter of controversy in the kidney. CD11/CD18 and intercellular adhesion molecule-1 blockade are usually protective in experimental renal IRI (9,12). In contrast, induction of systemic neutropenia and selectin function blockade do not have a protective effect, suggesting a neutrophil-independent mechanism for renal protection (6).…”

Section: Discussionmentioning

confidence: 99%

“…Leukocyte adhesion molecules seem to facilitate polymorphonuclear neutrophils recruitment during reperfusion, being implicated as mediators of renal IRI (5,6). Complementary studies using mAb, antisense oligonucleotides, or gene "knockout" indicate that blockade of ␤2 integrins and/or intercellular adhesion molecule-1 attenuates IRI in some experimental models (7)(8)(9)(10)(11)(12)(13). Furthermore, it was proposed recently that T cells might also mediate IRI through the interaction with renal tubular epithelial cells (14).…”

mentioning

confidence: 99%

Renal Ischemia/Reperfusion Injury

Molina¹,

Úbeda²,

Escribese³

et al. 2005

Journal of the American Society of Nephrology

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Renal ischemia/reperfusion injury (IRI) is an important cause of acute renal failure. Cellular and molecular responses of the kidney to IRI are complex and not fully understood. ␤1 integrins localize to the basal surface of tubular epithelium interacting with extracellular matrix components of the basal membrane, including collagen IV. Whether preservation of tubular epithelium integrity could be a therapeutic approach for IRI was assessed. The effects of HUTS-21 mAb administration, which recognizes an activation-dependent epitope of ␤1 integrins, in a rat model of IRI were investigated. Preischemic HUTS-21 administration resulted in the preservation of renal functional and histopathologic parameters. Analyses of activated ␤1 integrins expression and focal adhesion kinase phosphorylation suggest that its deactivation after IRI was prevented by HUTS-21 treatment. Moreover, HUTS-21 impaired the inflammatory response in vivo, as indicated by inhibition of proinflammatory mediators and the absence of infiltrating cells. Ex vivo adhesion assays using reperfused kidneys revealed that HUTS-21 induced a significant increase of epithelial cell attachment to collagen IV. In conclusion, the data provide evidence that HUTS-21 has a protective effect in renal IRI, preventing tubular epithelial cell detachment by preserving activated ␤1 integrins functions.

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“…ICAM-1 knockout mice appeared resistant to acute renal ischemic injury (89). Similarly, anti-CD11a and antiCD11b antibodies decreased injury after experimental renal ischemia in the rat (94). Furthermore, mice deficient for the Src-family kinases Hck and Fgr, required for integrin signal transduction, were resistant to the lethal effects of LPS-injection and had a marked reduction in renal damage (95).…”

Section: Inhibition Of Leukocyte Adhesionmentioning

confidence: 99%