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

During the ischemia/reperfusion phenomenon, adhesion molecules seem to play a critical role in the recruitment of neutrophils to sites of eventual tissue injury. E-selectin is an endothelium-derived molecule that mediates adhesion of neutrophils to activated endothelial cells. In vitro expression of E-selectin, after exposure to stimuli such as endotoxin, interleukin 1, or tumor necrosis factor alpha is maximal at 4 to 6 h, followed by a decline toward basal levels at 24 to 48 h. Characterizing the temporal expression of E-selectin in an in vivo model of skin flap ischemia-reperfusion would help to determine the optimal approach to eventual pharmacologic blockade. This intervention may prove therapeutically beneficial in attenuating flap injury. This study, using the standard porcine buttock skin flap model, was designed to evaluate immunohistochemically the expression of E-selectin in flaps subjected to (1) arterial ischemia (8 h)-reperfusion (18 h), (2) venous ischemia (8 h)-reperfusion (18 h), and (3) distal ischemia (26 h). Four flaps were examined per group, with 8 biopsies being collected sequentially over the 26-h study period from each flap. Blinded, semi-quantitative histologic scoring revealed the following results: (1) E-selectin is absent in normal porcine skin; (2) with arterial ischemia/reperfusion, E-selectin expression in flaps was maximal at 1 h of reperfusion, declining thereafter; (3) with venous ischemia/reperfusion, E-selectin expression peaked during the first hour of ischemia, with subsequent decline; and (4) within a flap designed to sustain distal ischemia, E-selectin expression is relatively more intense in regions of the flap distant from the vascular pedicle, and maximal at 6 h after flap elevation. Our conclusion, therefore, is that the kinetics of E-selectin expression within the tissues of porcine skin flaps differs depending on the type of ischemic insult sustained. Interpretation of these findings, correlating possible pathophysiologic differences in the different models of ischemia, is offered.
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PMID:Kinetics of E-selectin expression in surgical flaps. 951 61

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.
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PMID:Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults. 941 64

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.
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PMID:Soluble adhesion molecules in CSF are increased in children with severe head injury. 981 34

Products of enteric bacteria, including endotoxin [lipopolysaccharide (LPS)], have been implicated in the acute inflammatory responses elicited by ischemia and reperfusion (I/R) of the small intestine. The objective of this study was to assess the contribution of LPS to the increased E-selectin expression observed in the intestinal vasculature after I/R. The dual radiolabeled monoclonal antibody technique was used in LPS-sensitive (C3HeB/FeJ) and LPS-insensitive (C3H/HeJ) mice that were exposed to either exogenous LPS or to gut I/R (45 min ischemia, 5 h reperfusion). LPS elicited a dose-dependent (0.5-50 microgram LPS/animal) increase in E-selectin expression (at 3 h) in LPS-sensitive mice, whereas LPS-insensitive mice were largely unresponsive. E-selectin expression was increased fivefold by I/R in the small bowel of both LPS-sensitive and -insensitive mice. These results indicate that, although exogenous LPS is capable of eliciting profound dose-dependent increases in E-selectin expression, endogenous LPS does not contribute significantly to I/R-induced expression of this endothelial cell adhesion molecule.
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PMID:Role of endotoxin in intestinal reperfusion-induced expression of E-selectin. 995 Aug 22

There is increasing evidence that the inflammatory response plays an important role in CNS ischemia. The murine model of focal ischemia, however, remains incompletely characterized. In this study we examined expression of several cytokines and the vascular adhesion molecule E-selectin, in order to characterize the molecular events following stroke in the C57BL/6J mouse. Using a multi-probe RNAse protection assay (RPA), mRNA for 19 cytokines was analyzed following permanent and transient occlusion of the middle cerebral artery in mice. In addition, samples from the same mice were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate E-selectin mRNA expression levels. Several cytokine mRNAs showed a similar expression pattern in both permanent and transient CNS ischemia while others showed a temporal expression pattern that was dependent on the type of stroke. For both models, mRNA levels of TNFalpha rose early (4 h) followed by IL-6 (10-18 h) and a comparatively late increase (96 h) in TGFbeta1. IL-1alpha, IL-1beta and IL-1ra levels showed a model dependent shift in temporal expression. Reperfusion appeared to delay the induction of these cytokines. Temporal changes in cytokine mRNA expression in the mouse CNS occur following ischemic damage. Our findings demonstrate the utility and power of multi-probe RPA for evaluation of changes in cytokine mRNA levels. Moreover, this study is, to our knowledge the first to show temporal changes in cytokine mRNA in mouse cerebral ischemia, forming a basis for further exploration of the roles of these cytokines in modulating ischemic neuronal damage in this model.
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PMID:Temporal modulation of cytokine expression following focal cerebral ischemia in mice. 1002 29

The plasma levels of interleukin 1 beta (IL 1beta), interleukin 6 (IL 6), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF-alpha), E-selectin, ICAM 1 and C-reactive protein (CRP) have been studied in 24 patients with acute myocardial infarction in the course of 96 h. The plasma IL 1beta and IL 6 levels were continually elevated during the 96 h study period (the peak of plasma IL 1beta level was 22.2 pg/ml, S.D. 8.6, P < 0.001, normal values of IL 1beta are less than 10 pg/ml, the mean peak plasma concentration of IL 6 was 184.9 pg/ml, S.D. 134.7, vs. normal values of 15.57 pg/ml, S.D. 2.4, P < 0.001). The mean plasma IL 8 level was increased for the duration of the study, the mean plasma IL 8 level was 103.0 pg/ml, S.D. 23.4 (normal value was below 30 pg/l, S.D. 8.0) P < 0.001. The plasma TNF-alpha level was elevated throughout the time of observation without any significant peak. The mean plasma TNF-alpha concentration was 46.8 pg/ml, S.D. 2.13, vs. normal value 4.35 pg/ml, S.D. 1.23, P < 0.001. The plasma E-selectin level reached the mean level of 145.1 ng/ml, S.D. 75.4, vs. normal value 29.1-63.4 ng/ml, P < 0.001 at an interval of 15-42 h after the onset of the symptoms. The plasma ICAM 1 level showed only a slight significant increase during the first 36 h. The plasma CRP concentration increased later than IL 6, and reached a peak at 42 h after the onset of the symptoms (69.2 mg/l, S.D. 29.9, vs. 1.2 mg/l, S.D. 4.7, P < 0.0001). We conclude that cytokines and adhesion molecules can play an important role in the mechanisms of tissue injury in the process of ischemia and reperfusion.
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PMID:Cytokines and adhesion molecules in the course of acute myocardial infarction. 1009 May 30

We examined brain sections from P- and E-selectin-deficient mice (-/-) and their nontransgenic littermates (+/+) after focal cerebral ischemia and reperfusion (I/R) tissue injury. There was no difference in the subsequent infarct volume after 3 h of ischemia and 21 h of reperfusion. These data indicate that selectin-independent mechanisms mediate tissue injury after a prolonged period of transient focal ischemia.
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PMID:P- and E-selectin-deficient mice are susceptible to cerebral ischemia-reperfusion injury. 1041 96

Leucocyte migration into lymphatic tissues or inflammatory sites depends upon the expression of adhesion molecules. Among these molecules, the selectins expressed on endothelial cells (E- and P-selectins) and leucocytes (L-selectin) recognize carbohydrate ligands such as sialyl Lewis A or sialyl Lewis X oligosaccharides due to the same positioning of NeuAc, Gal and Fuc residues in both isomeric structures. We have shown that the sialic acid residue could be replaced by a sulfate group such as in the sulfated Lewis A pentasaccharide, one of the most potent monovalent ligand for human E-selectin, which was shown to be very active in the prevention of ischemia reperfusion lung injury. In the same way, we have prepared through chemoenzymatic syntheses, two disulfated Lewis X pentasaccharides, the sulfated analogs of carbohydrate ligands found on GLYCAM 1, the natural receptor of L-selectin. Finally, based on the double recognition of L-selectin with Lewis type and glycosaminoglycan structures, we tentatively introduced a possible link between the selectin- and the integrin-mediated lymphocyte adhesion systems.
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PMID:[Oligosaccharide sulfate inhibitors of selectin-sugar interactions in inflammatory processes]. 1042 56

Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This 'ischemic preconditioning' is ascribed to various mechanisms, including oxidative stress. We investigated whether preconditioning exists on an endothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H(2)O(2), 5 min). Adhesion molecules ICAM-1 and E-selectin and release of cytokines IL-6 and IL-8 to subsequent stimulation with TNF-alpha (2.5 ng/ml, 4 h) were measured (flow cytometry and immunoassay), as were nuclear translocation of the transcription factor NFkappaB (Western blotting, confocal microscopy) and redox status of HUVECs (quantification of glutathione by HPLC). TNF-alpha elevated IL-6 in the cell supernatant from 8.8 +/- 1 to 41 +/- 3 pg/ml and IL-8 from 0.5 +/- 0. 03 to 3 +/- 0.2 ng/ml. ICAM-1 was increased threefold and E-selectin rose eightfold. Oxidative stress (decrease of glutathione by 50%) reduced post-TNF-alpha levels of IL-6 to 14 +/- 3 and IL-8 to 1 +/- 0.2; the rise of ICAM-1 was completely blocked and E-selectin was only doubled. The anti-inflammatory effects of preconditioning via oxidative stress were paralleled by reduction of the translocation of NFkappaB on stimulation with TNF-alpha, and antagonized by the intracellular radical scavenger N-acetylcysteine. 'Anti-inflammatory preconditioning' of endothelial cells by oxidative stress may account for the inhibitory effects of preconditioning on leukocyte adhesion in vivo.
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PMID:Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-alpha. 1069 71

The effects of two chemically unrelated nitric oxide (NO)-releasing compounds were studied on adhesion molecule expression in and neutrophil adhesion to human umbilical vein endothelial cells. Incubation of confluent monolayers of endothelial cells with increasing concentrations of lipopolysaccharide stimulated the adhesion of polymorphonuclear leukocytes to endothelial cells. Flow cytometric analysis showed that lipopolysaccharide treatment upregulated the expression of adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells. A novel NO-releasing compound GEA 3175 (1,2,3, 4-oxatriazolium, -3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) inhibited lipopolysaccharide-induced adhesion being more potent than the earlier known NO donor S-nitroso-N-acetylpenicillamine. The increased E-selectin expression induced by lipopolysaccharide was significantly attenuated by the two NO donors tested whereas ICAM-1 expression remained unaltered. The present data show that NO donors inhibit E-selectin expression in and neutrophil adhesion to lipopolysaccharide-stimulated vascular endothelial cells. Thus, by inhibiting leukocyte adhesion NO donors may reduce leukocyte infiltration and leukocyte-mediated tissue injury in inflammation and ischemia-reperfusion injury.
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PMID:Inhibition by nitric oxide-releasing compounds of E-selectin expression in and neutrophil adhesion to human endothelial cells. 1077 Oct 47


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