The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion (original) (raw)
Related papers
Quantification of P-Selectin Expression After Renal Ischemia and Reperfusion* 1
Journal of pediatric …, 1997
Neutrophils are important in ischemia and reperfusion injury. Multiple factors may be responsible for the adhesion of granulocytes to endothelial cells. P-selectin is a carbohydrate-binding glycoprotein that is stored preformed in endothelial cells as Weibel-Palade bodies. This preformation ...
Small molecule selectin ligand inhibition improves outcome in ischemic acute renal failure
Kidney International, 2001
Small molecule selectin ligand inhibition improves outcome in genesis of renal ischemia-reperfusion injury (IRI) have ischemic acute renal failure. most commonly utilized the model of renal artery clamp-Background. The pathophysiologic and potential therapeuing. Post-ischemic renal injury in this model has been tic role of selectins in renal ischemia-reperfusion injury (IRI) shown to be very similar to human ischemic renal injury, is not fully understood, due in part to redundancy in the roles including that secondary to cold kidney storage prior to of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule (TBC-1269) transplantation [5, 6]. However, a recent review also has would improve the course of renal IRI by overcoming redunemphasized differences between experimental animal dancy issues. This was investigated in a rat model of renal IRI. and human acute renal failure [7]. Methods. Rats were treated with TBC-1269 either during Several studies have shown that ischemia-reperfusion or post-IRI. The effects of TBC-1269 were investigated in two can stimulate renal expression of leukocyte adhesion models of renal IRI: moderate IRI (30 minutes bilateral renal artery clamping) and severe IRI (45 minutes clamping). The molecules [8, 9]. Previous studies have demonstrated combination of anti-E-and anti-P-selectin antibodies also was that antibody blockade of the CD11/CD18 receptor on investigated in rats subjected to moderate IRI. Renal function, leukocytes significantly attenuated renal IRI in rats histological injury and mortality were assessed.
The American Journal of Pathology, 2007
Leukocyte infiltration into inflamed tissues is considered to involve sequential steps of rolling over the endothelium, adhesion, and transmigration. In this model, the leukocyte adhesion molecule L-selectin and its ligands expressed on inflamed endothelial cells are involved in leukocyte rolling. We show that upon experimental and human renal ischemia/reperfusion, associated with severe endothelial damage, microvascular basement membrane (BM) heparan sulfate proteoglycans (HSPGs) are modified to bind L-selectin and monocyte chemoattractant protein-1. In an in vitro rolling and adhesion assay, L-selectin-binding HSPGs in artificial BM induced monocytic cell adhesion under reduced flow. We examined the in vivo relevance of BM HSPGs in renal ischemia/reperfusion using mice mutated for BM HSPGs perlecan (Hspg2 ⌬3/⌬3), collagen type XVIII (Col18a1 ؊/؊), or both (crossbred Hspg2 ⌬3/⌬3 ؋Col18a1 ؊/؊) and found that early monocyte/macrophage influx was impaired in Hspg2 ⌬3/⌬3 ؋Col18a1 ؊/؊ mice. Finally, we confirmed our observations in human renal allograft biopsies, showing that loss of endothelial expression of the extracellular endosulfatase HSulf-1 may be a likely mechanism underlying the induction of L-selectinand monocyte chemoattractant protein-1-binding HSPGs associated with peritubular capillaries in human renal allograft rejection. Our results provide evidence for the concept that not only endothelial but also (microvascular) BM HSPGs can influence inflammatory responses.
Journal of Clinical Investigation, 1997
Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (Յ 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNF ␣ , IFN ␥) and macrophage-associated products (IL-1, IL-6, TGF ) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand (sPSGL) was used. Ischemic kidneys were perfused in situ with 5 g of sPSGL in UW solution; 50 g was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P-and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.
Journal of Experimental Medicine, 1999
Resuscitation from hemorrhage induces profound pathophysiologic alterations and activates inflammatory cascades able to initiate neutrophil accumulation in a variety of tissues. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that significant leukocyte–endothelium interactions occur very early in other forms of ischemia/reperfusion (i.e., splanchnic ischemia/reperfusion and traumatic shock) which are largely mediated by increased expression of the adhesion molecule, P-selectin, on the vascular endothelium. Here we postulated that increased endothelial expression of P-selectin in the microvasculature would play an essential role in initiating the inflammatory signaling of hemorrhagic shock. Using intravital microscopy, we found that hemorrhagic shock significantly increased the number of rolling and adherent leukocytes in the mouse splanchnic microcirculation. In contrast, mice genetically deficient in P-selectin, or wild-typ...
Hepatology, 1999
Hepatic damage following ischemia-reperfusion injury involves polymorphonuclear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene-targeted deficient mice, we evaluated P-selectin and its contribution to PMN and platelet adhesion in hepatic damage. In an in vivo warm ischemia model, hepatic injury was assessed by serum transaminase levels, survival, PMN adhesion by histological analysis, and platelet sequestration by immunostaining. Serum transaminase levels were strikingly reduced (by up to threefold) in the P-selectin deficient mice, particularly at 90 minutes of ischemia, when compared with wild-type controls. PMN adhesion and platelet sequestration was also significantly decreased in P-selectin deficient mice following 90 minutes of partial ischemia. Animal survival was significantly improved after 75 minutes of total hepatic ischemia in P-selectin deficient mice when compared with wild-type mice. Survival was also achieved after 90 minutes of ischemia in the mutant mice whereas none of the wild-type animals survived. These data show that P-selectin plays a critical role in PMN and platelet adhesion following ischemia-reperfusion injury to the liver. (HEPATOLOGY 1999; 29:1494-1502.)