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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine whether the microvascular responses to ischemia and reperfusion (I/R) are altered in an animal model of atherosclerosis, the low-density lipoprotein-receptor knockout (LDLr -/-) mouse. Intravital video microscopy was used to monitor venular wall shear rate, leukocytes rolling velocity, the number of rolling, adherent and emigrated leukocytes, and albumin leakage in cremasteric postcapillary venules of wild-type (B6129) and LDLr -/- mice exposed to 60 min of ischemia and 60 min of reperfusion. The postcapillary venules of LDLr -/- mice exhibited two- to threefold larger increments in the number of adherent leukocytes and a more profound albumin leakage response to I/R than venules in wild-type mice. The exaggerated inflammatory responses noted in LDLr -/- mice placed on a normal diet were not exacerbated by a high-cholesterol diet. Treatment of LDLr -/- mice with either a platelet-activating factor (PAF) receptor antagonist (WEB-2086) or a monoclonal antibody (YN-1) against the endothelial cell adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), markedly attenuated the I/R-induced leukocyte adherence and albumin leakage. These findings indicate that atherogenic mice are more vulnerable to the deleterious microvascular effects of I/R and that PAF-mediated, ICAM-1-dependent leukocyte adhesion contributes to this exaggerated response to I/R.
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PMID:Ischemia-reperfusion induced microvascular responses in LDL-receptor -/- mice. 1033 Feb 50

In many diseases and acute inflammatory disorders, important components of pathological processes are linked to the neutrophils' ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissue. This review summarizes the mechanisms of tissue destruction by neutrophils and the role of kidney-specific factors that promote this effect. Nicotinamide adenine dinucleotide phosphate H (NADPH) oxidase is a membrane-associated enzyme that generates a family of reactive oxygen intermediates (ROI). There is increasing evidence that ROIs are implicated in glomerular pathophysiology: ROIs contribute to the development of proteinuria, alter glomerular filtration rate, and induce morphological changes in glomerular cells. Specific neutrophil granules contain microbicidal peptides, proteins, and proteolytic enzymes, which mediate the dissolution of extracellular matrix, harm cell structures or cell function, and induce acute and potentially irreparable damage. Although both ROI and neutrophil-derived proteases alone have the potential for tissue destruction, it is their synergism that circumvents the intrinsic barriers designed to protect the host. Even small amounts of ROI can generate hypochlorus acid (HOCl) in the presence of neutrophil-derived myeloperoxidase (MPO) and initiate the deactivation of antiproteases and activation of latent proteases, which lead to tissue damage if not properly controlled. In addition, neutrophil-derived phospholipase products such as leukotrienes and platelet-activating factor contribute to vascular changes in acute inflammation and amplify tissue damage. Increasing evidence suggests that mesangial cells and neutrophils release chemotactic substances (eg, interleukin 8), which further promote neutrophil migration to the kidney, activate neutrophils, and increase glomerular injury. Also, the expression of adhesion molecules (eg, intercellular adhesion molecule 1 on kidney-specific cells and beta-2-integrins on leukocytes) has been correlated with the degree of injury in various forms of glomerulonephritis or after ischemia and reperfusion. Together, these results suggest that neutrophils and adhesion molecules play an important role in mediating tissue injury with subsequent renal failure. Conversely, chronic renal failure reduces neutrophil function and thereby can increase susceptibility to infection and sepsis.
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PMID:Neutrophils and renal failure. 1043 Sep 93

Recent studies have shown a crucial role of intercellular adhesion molecule 1 (ICAM-1) in expansion of infarction after focal cerebral ischemia. The purpose of the present study was to assess whether ICAM-1 is involved in selective neuronal vulnerability and reactive gliosis after transient forebrain ischemia. ICAM-1 knockout mice and wild-type mice were subjected to transient forebrain ischemia for 5, 10 or 15 min, and the hippocampus and caudoputamen were examined 7 days later with conventional histological and immunohistochemical methods. Bilateral common carotid artery occlusion with less than 10% of baseline cortical microperfusion for 10 or 15 min resulted in ischemic neuronal damage in the hippocampus and caudoputamen. The frequency and the severity of neuronal damage were similar in wild-type and knockout mice. Proliferation of reactive astrocytes in the hippocampus was also similar in both types of mice. Therefore, it is highly unlikely that ICAM-1 plays a key role in delayed neuronal death after transient global ischemia or in astroglial responses after ischemic neuronal injury.
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PMID:Deficiency of intercellular adhesion molecule 1 fails to mitigate selective neuronal death after transient global ischemia. 1057 85

Reperfusion damage is largely due to the adherence of polymorphonuclear leukocytes to the endothelium initiated by adhesion molecule upregulation. The reduced endothelial nitric oxide release during ischemia may be involved in the upregulation of intercellular adhesion molecule 1. In this study, we tested if nitric oxide donors suppress polymorphonuclear leukocyte adherence to activated endothelial cells by inhibition of the intercellular adhesion molecule 1 surface expression. Confluent human umbilical vein endothelial cells were stimulated with tumor necrosis factor alpha (300 U/mL) after preincubation with increasing concentrations of the nitric oxide donors CAS 1609 (0.005-5 mM/L) and 3-(4-morpholinyl)-sydnonimine (0.01-1 mM/L). Intercellular adhesion molecule 1 surface expression was measured in a cell surface enzyme-linked immunosorbent assay, intercellular adhesion molecule 1 mRNA by Northern analysis. Human saphenous vein endothelial cells were transfected with the inducible nitric oxide synthase gene and stimulated with tumor necrosis factor alpha (300 U/mL). Fluorescein green-labeled polymorphonuclear leukocytes adhering to activated human umbilical vein endothelial cells/human saphenous vein endothelial cells were quantified by epifluorescent microscopy. The intercellular adhesion molecule 1 surface expression of activated human umbilical vein endothelial cells/human saphenous vein endothelial cells was significantly diminished to 40 to 60% of the maximum after treatment with CAS 1609, 3-(4-morpholinyl)-sydnonimine, or transfection with the inducible nitric oxide synthase gene. Intercellular adhesion molecule 1 mRNA was diminished by CAS 1609 and 3-(4-morpholinyl)-sydnonimine in the same manner. The functional relevance of our data was shown by reduction of polymorphonuclear leukocyte adherence to activated human umbilical vein endothelial cells/human saphenous vein endothelial cells following treatment with CAS 1609 and 3-(4-morpholinyl)-sydnonimine or transfection with inducible nitric oxide synthase. Tumor necrosis factor-induced polymorphonuclear leukocyte adherence was abolished by blocking antibody against intercellular adhesion molecule 1. Thus, exogenous or endogenous substitution of nitric oxide diminishes the expression of endothelial intercellular adhesion molecule 1 and its mRNA following tumor necrosis factor alpha stimulation. This results in a reduced polymorphonuclear leukocyte adherence to activated endothelium.
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PMID:NO reduces PMN adhesion to human vascular endothelial cells due to downregulation of ICAM-1 mRNA and surface expression. 1068 Jun 42

We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of A(2A) adenosine receptors (A(2A)-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective A(2A)-AR agonist, was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice via osmotic minipumps, and animals were subjected to I/R. I/R led to an increase in plasma creatinine and kidney neutrophil infiltration. Infusion of DWH-146e at 10 ng. kg(-1). min(-1) produced a 70% reduction in plasma creatinine as well as a decrease in neutrophil density in outer medulla and cortex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase activity in kidney correlated with the degree of renal injury. P-selectin and intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most prominent in endothelial cells of peritubular capillaries and interlobular arteries of cortex and outer and inner medulla of vehicle-treated mice whose kidneys were subjected to I/R. DWH-146e treatment led to a pronounced decrease in P-selectin- and ICAM-1-like immunoreactivity. These data are consistent with our hypothesis that A(2A)-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion.
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PMID:A(2A) adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion. 1105 40

To elucidate a role of costimulatory molecule and cell adhesion molecule in hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD80), B7-2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expression in the rat liver after warm ischemia/reperfusion injury. To induce hepatic warm ischemia in a rat model, both portal vein and hepatic artery entering the left-lateral and median lobes were occluded by clamping for 30 minutes or 60 minutes, and then reperfused for 24 hours. B7-1, B7-2, and ICAM-1 expressions in the liver were analyzed by immunofluorescence staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Although B7-1 and B7-2 expressions were at very low levels in the liver tissues from normal or sham-operated control rats, both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA) levels in the affected, left lobes after warm ischemia/reperfusion. ICAM-1 protein and mRNA were constitutively expressed in the liver of normal and sham-operated control rats, and further up-regulated after warm ischemia/reperfusion. Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von Willebrand factor as a marker protein for endothelial cells, was confined by immunofluorescence staining to sinusoidal endothelial cells in hepatic lobules. Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA levels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and 52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was rather constitutive but further enhanced by warm ischemia/reperfusion (4.24-fold increase). These results suggest that hepatic sinusoidal endothelial cells play a pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm hepatic ischemia/reperfusion injury, and that B7-1 and/or B7-2 might be the primary target to prevent early rejection and inflammatory reactions after hepatic ischemia/reperfusion injury associated with liver transplantation.
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PMID:Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver. 1158 72

Recent studies suggested that the vascular endothelial cells function as a resident antigen-presenting cell (APC) in certain situations such as organ transplantation, and the ischemia/reperfusion injury, an inevitable event in organ transplantation, leads to an enhanced biosynthesis of cell adhesion molecules. We have demonstrated that the hepatic sinusoidal endothelial cells have potential ability as APCs by expressing the costimulatory adhesion molecule proteins, CD80 (B7-1) and CD86 (B7-2), of which expression was enhanced by warm ischemia/reperfusion of the rat liver. In this study, we assessed the localization of CD80, CD86, and intercellular adhesion molecule 1 in the rat kidneys and the influence of warm ischemia/reperfusion with or without a hypercreatinemic condition on the expression of these adhesion molecules in the renal tissues. Wistar male rats weighing 150 to 230 g were divided into group A, receiving a sham-operation (control), group B, receiving 1-hour clamping of the left renal pedicle (temporary ischemia), and group C, receiving right nephrectomy and 1-hour clamping of the left renal pedicle (temporary ischemia with hypercreatinemia). The left kidneys were submitted to immunohistochemical and molecular analyses sequentially for the period of 14 days. We found that CD80, CD86, and intercellular adhesion molecule 1 proteins localized on the glomerular and peritubular endothelium and were up-regulated after ischemia/reperfusion. The up-regulation of these three proteins was enhanced by the hypercreatinemic condition. The relative mRNA levels analyzed by real-time reverse transcription polymerase chain reaction showed that CD80 and CD86 expressions were constitutively observed and significantly increased for 14 days after the warm ischemia reperfusion with a peak level at Day 3 (6.7- and 20.8-fold increase for CD80 and CD86, respectively). Our results suggested that the glomerular endothelial cells will play a pivotal role as a APC by expressing CD80 and CD86 in the induction of renal tissue injury associated with the ischemia/reperfusion at renal transplantation surgery, as well as the peritubular endothelium.
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PMID:Glomerular endothelium exhibits enhanced expression of costimulatory adhesion molecules, CD80 and CD86, by warm ischemia/reperfusion injury in rats. 1221 82

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-kappaB (NF-kappaB) has been implicated in this process, we treated rats with vehicle or the IkappaB-alpha inhibitor BAY 11-7085 (25 mg/kg ip) 1 h before mesenteric ischemia-reperfusion (45 min of ischemia followed by reperfusion at 30 min or 6 h) and examined the ileal injury response. Vehicle-treated rats subjected to ischemia-reperfusion exhibited severe mucosal injury, increased myeloperoxidase (MPO) activity, increased expression of interleukin-6 and intercellular adhesion molecule 1 protein, and a biphasic peak of NF-kappaB DNA-binding activity during the 30-min and 6-h reperfusion courses. In contrast, BAY 11-7085-pretreated rats subjected to ischemia-reperfusion exhibited less histological injury and less interleukin-6 and intercellular adhesion molecule 1 protein expression at 30 min of reperfusion but more histological injury at 6 h of reperfusion than vehicle-treated rats subjected to ischemia-reperfusion. Studies with phosphorylation site-specific antibodies demonstrated that IkappaB-alpha phosphorylation at Ser(32),Ser(36) was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IkappaB-alpha was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas alpha-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IkappaB-alpha. Thus NF-kappaB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.
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PMID:Effects of NF-kappa B inhibition on mesenteric ischemia-reperfusion injury. 1246 47

Ischemia/reperfusion (I/R) occurs in a number of pathological conditions, including myocardial infarction, stroke, and organ transplantation. During the reperfusion phase, leukocytes are recruited into affected tissues, where they can cause tissue damage and organ failure. Various in vitro models have been developed to study the role of adhesion molecules in I/R-mediated leukocyte recruitment. These models traditionally use isolated leukocytes and static conditions and, therefore, may not recapitulate the in vivo situation. We developed two novel in vitro models of I/R-mediated leukocyte recruitment in which leukocyte recruitment was examined using whole blood under shear conditions. Chemical treatments were used to mimic I/R in the first model, while sequential exposure to hypoxia/reoxygenation (H/R) was used to mimic I/R in the second model. We found that leukocytes were recruited from whole blood under shear conditions to endothelial cells treated with chemically induced I/R or H/R. In both models, mRNA for intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin was upregulated. The role of adhesion molecules in leukocyte recruitment differed slightly between the two models, with E-selectin and VCAM-1 playing approximately equal roles in leukocyte recruitment in the chemically induced I/R model and VCAM-1 being a central mediator of leukocyte recruitment in the H/R model.
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PMID:Ischemia/reperfusion induces the recruitment of leukocytes from whole blood under flow conditions. 1508 64

In the present study, we used glucocorticoid-induced tumor necrosis factor (TNF) receptor family gene knockout (GITR-KO) mice to evaluate a possible role of GITR on the pathogenesis of splanchnic artery occlusion (SAO) shock, which was induced in mice by clamping the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the lipid peroxidation in the ileum of the SAO-shocked, GITR wild-type (WT) mice after reperfusion. The absence of GITR significantly reduced the lipid peroxidation in the intestine. SAO-shocked WT mice developed a significant increase of ileum tissue, TNF-alpha, and myeloperoxidase activity and marked histological injury. SAO shock was also associated with a significant mortality (5% survival at 24 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin, intercellular adhesion molecule 1 (ICAM-1), and E-selectin. The intensity and degree of P-selectin, E-selectin, and ICAM-1 were markedly reduced in tissue section from SAO-shocked, GITR-KO mice. SAO-shocked, GITR-KO mice also showed a significant reduction of the TNF-alpha production and neutrophil infiltration into the reperfused intestine, an improved histological status of the reperfused tissues, and an improved survival. Taken together, our results clearly demonstrate that GITR plays an important role in the ischemia and reperfusion injury and put forward the hypothesis that modulation of GITR expression may represent a novel and possible strategy.
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PMID:Glucocorticoid-induced TNF receptor family gene (GITR) knockout mice exhibit a resistance to splanchnic artery occlusion (SAO) shock. 1531 36


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