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

The effects of glucocorticoid (GC) on ischemic brain remain to be investigated. Since GC modulates immunological system, it also may inhibit macrophage accumulation in the ischemic brain. The GC effect, if any, on macrophages in ischemic brain, may be mediated through modulation of JE/MCP-1 gene, a strong monocyte attractant, which is expressed in the rat brain after ischemia. The purpose of the present study is to elucidate the effect of high dose methylprednisolone (MP) treatment on (1) macrophage infiltration, (2) histopathology of the ischemic lesion, and (3) expression of JE/MCP-1 mRNA, in a focal cerebral ischemia model of the rat. Thirty Wistar rats were used in this study. Focal cerebral ischemia was induced by advancing a nylon monofilament into the internal carotid artery until the origin of the middle cerebral artery (MCA) was occluded. For JE/MCP-1 mRNA study, animals (n = 9) were randomly injected with MP 75 mg/kg (x 3) (n = 3), 100 mg/kg (x 3) (n = 3), or same volume of saline (n = 3) and killed 24 h after onset of MCA occlusion. Three animals were used as a normal control, and a section of the liver from one rat was used as an internal control for JE/MCP-1 mRNA. Northern blot analysis was performed using murine JE c-DNA. For the histopathological study, animals (n = 17) were randomly divided into a MP group (MP 100 mg/kg x 3, n = 9) and a control group (saline treated, n = 8), and killed 72 h after onset of MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High dose methylprednisolone therapy reduces expression of JE/MCP-1 mRNA and macrophage accumulation in the ischemic rat brain. 772 31

The myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
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PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

Central nervous system injuries such as focal brain ischemia and trauma are known to initiate inflammatory reactions. To demonstrate the involvement of adhesion molecules in these inflammatory responses, we have observed significant increases of ICAM-1 and ELAM-1 mRNA expression in the ischemic cortex of rats by means of Northern blot analysis and/or semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). In the ischemic cortex, levels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, p < 0.05), peaked at 6 to 12 h (6.0-fold, p < 0.01), and remained elevated for up to 5 days (2.5-fold, p < 0.05) after permanent occlusion of the middle cerebral artery (PMCAO). The basal expression of ELAM-1 mRNA was extremely low (undetectable by Northern analysis). Following focal ischemia, however, ELAM-1 mRNA was markedly increased at 6 h in the ischemic cortex, peaked at 12 h (6.4-fold increase compared to sham samples, p < 0.01), and then returned to almost basal levels by 5 days post-PMCAO. Immunohistochemical stainings using anti-ICAM-1 antibodies demonstrated a marked increase of ICAM-1 in the ischemic cortex over the nonischemic cortex or the sham-operated samples. The immunoreactive ICAM-1 signal was localized to endothelial cells of intraparenchymal blood vessels in the ischemic cortex. Furthermore, time-course analysis demonstrated that the increased expression of ICAM-1 and ELAM-1 parallel those of chemokines such as KC and MCP-1, but are more delayed than those of inflammatory cytokines including TNF-alpha and IL-1 beta, which are known to induce expression of ICAM-1 and ELAM-1 on endothelial cells. The upregulation of the inflammatory genes and their products precedes leukocytes' adhesion to endothelial cells and their migration into the ischemic tissue, suggesting that these upregulated adhesion molecules on brain capillary endothelium play an important role in leukocyte migration into ischemic brain tissue.
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PMID:Induced expression of adhesion molecules following focal brain ischemia. 859 10

Cell surface assembly of the membrane attack complex (MAC) of complement occurs in a variety of pathophysiological settings. Depending upon the density and size distribution of pores formed by the MAC and the functional integrity of membrane regulators of complement activation, the MAC can either cause direct cell lysis or transduce cell activation. We have examined the functional capacity of sublytic concentrations of MAC to induce the secretion of specific alpha- and beta-chemokines from human umbilical vein endothelial cells (HUVECs). Endothelial cell activation by the MAC has particular relevance to complement-dependent inflammatory processes including ischemia-reperfusion injury and acute lung injury. Assembly of sublytic concentrations of the MAC on HUVECs resulted in the sequential secretion of both neutrophil and monocyte chemotactic activities. Analysis of conditioned medium from MAC-bearing HUVECs revealed that the neutrophil chemotactic activity was largely attributable to interleukin (IL)-8, whereas the monocyte chemotactic activity, which was detected later (peak at 8 hours versus 4 hours), was largely attributable to MCP-1. This temporal pattern of MAC-induced secretion of IL-8 and MCP-1 was confirmed using IL-8- and MCP-1-specific enzyme-linked immunosorbent assays. Northern hybridization analysis of HUVECs revealed that MAC deposition was accompanied by an increase in IL-8 and MCP-1 mRNA levels. These data indicate that assembly of sublytic concentrations of the MAC on HUVECs can induce the sequential secretion of both neutrophil and monocyte chemotactic activities and that the former is largely attributable to IL-8 whereas the latter is largely attributable to MCP-1.
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PMID:The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells. 878 Mar 99

MCAF (monocyte chemotactic and activating factor)/MCP-1 (monocyte chemoattractant protein-1) is an important mediator of monocyte recruitment to inflammatory sites. However, its pathophysiologic role in myocardial reperfusion injury remains unknown. Male Wistar rats were anesthetized, and the left anterior descending coronary artery was ligated for an hour, after which the ligature was released. Northern blotting analysis revealed that MCAF/MCP-1 mRNA expression increased 16-fold in the reperfused region at 12 hours after reperfusion. MCAF/MCP-1 concentration in plasma and the heart was already elevated after hour of ischemia in this model. Goat polyclonal antibodies were prepared by repeated immunization of animals with purified, recombinant rat MCAF/MCP-1, and the neutralizing activities of this antibody were confirmed by monocyte chemotaxis assay and administration to rats with crescentic glomerulonephritis. Intravenous injection of anti-MCAF/MCP-1 antibody significantly reduced the infarct size at 24 hours after reperfusion compared with the injection of control IgG (33.9 +/- 5.1% vs 49.4 +/- 2.7% of ischemic area, mean +/- SEM). Administration of this antibody markedly decreased the intercellular adhesion molecule-1 mRNA expression and infiltration of macrophages, which suggested the pathophysiologic role of MCAF/MCP-1. Neutralization of MCAF/MCP-1 is beneficial by preventing reperfusion injury in a rat model of myocardial ischemia and reperfusion.
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PMID:Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. 1006 7

The adherence of activated neutrophils to endothelial cells during ischemia/reperfusion injury is mediated by inside-out signal transduction. Subsequently, outside-in signal transduction occurs following ligation of adhesion molecules with their ligands triggering respiratory bursts of neutrophils. In addition, neutrophil elastase enhances CC- and CXC-chemokine production by monocytes and macrophages. MCP-1, a CC-chemokine, enhances tissue factor production by macrophages and increases ICAM-1 expression on endothelial cells. Chemotaxis and respiratory bursts of neutrophils are augmented by CXC-chemokines. Furthermore, neutrophil elastase inactivates anticoagulants including antithrombin III, heparin cofactor II, and thrombomodulin, suggesting that neutrophil elastase aggravates microcirculatory disturbance after ischemia/reperfusion. Thus neutrophil elastase modulates the interation of neutrophils and endothelial cells during ischemia/reperfusion injury. Taken together with these observations, a therapeutic regimen with antibodies against adhesion molecules in combination with neutrophil elastase inhibitor and anticoagulants may attenuate ischemia/reperfusion injury.
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PMID:[Interaction between neutrophils and endothelial cells following ischemia/reperfusion]. 1041 50

The liver is an organ with abundant blood flow, consisting of hepatic arterial and portal blood flow. The viability of liver tissue depends on the condition of the hepatic microcirculation which is controlled by hepatic sinusoidal lining cells. Hepatic ischemia and reperfusion (HIR) injury is inevitable in surgical procedures for liver trauma and hepatectomy as well as liver transplantation. Reperfusion through an ischemically damaged organ enhances the tissue injury. Cytokines are pivotal factors in neutrophil-mediated liver injury following HIR, while various other mediators are involved in this insult. Advances in molecular biology have allowed the identification of various cytokines. Inflammatory cytokines such as TNF-alpha are associated with the induction of cellular adhesion molecules and hepatic microcirculatory impairment based on neutrophil-vascular endothelial cell interaction. Members of the chemokine family such as IL-8, CINC, MIP-2, and MCP-1 are involved in neutrophil infiltration in the liver and remote organs. Since each cytokine has a wide variety of actions and interacts' among others' via the cytokine network, their actions in HIR injury have not been determined completely. Kupffer cells have been focused on as a source of cytokine production in HIR injury. Further studies on the mechanisms of cytokine production after HIR and analysis of regulation in the cytokine network would clarify the pathophysiology of HIR injury and the most suitable therapeutic strategy for this insult.
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PMID:[Role of cytokines in hepatic ischemia and reperfusion injury]. 1041 51

To identify the mechanisms that cause monocyte localization in infarcted myocardium, we studied the impact of ischemia-reperfusion injury on the surface expression and function of the monocyte fibronectin (FN) receptor VLA-5 (alpha(5)beta(1) integrin, CD49e/CD29). Myocardial infarction was associated with the release of FN fragments into cardiac extracellular fluids. Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments. Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin. We postulated that changes in VLA-5 expression, which were induced by interactions with cell-binding FN fragments, may alter monocyte migration into tissue FN, a prominent component of the cardiac extracellular matrix. Support for this hypothesis came from experiments showing that FN120 treatment significantly reduced both spontaneous and MCP-1-induced monocyte migration on an FN-impregnated collagen matrix. In vivo, it is likely that contact with cell-binding FN fragments also modulates VLA-5/FN adhesive interactions, and this causes monocytes to accumulate at sites where the fragment concentration is sufficient to ensure proteolytic degradation of VLA-5.
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PMID:Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration. 1044 34

We have analyzed chemokine mRNA expression in graft tissue of C3H/HEJ mice receiving allogeneic (C57BL/6) or xenogeneic [Lewis (LEW) rat donors] kidney grafts and correlated this with graft survival. Since donor-specific portal vein (pv) immunization is known to increase allo- and xenograft survival, in some cases recipients also received pretransplant pv or intravenous (iv) immunization; other animals received the antioxidant N-acetylcysteine (NAc) to examine the role of ischemia/reperfusion injury in the changes observed. Graft tissue and lymph nodes draining the respective grafts were obtained at various times posttransplantation and used for quantitative polymerase chain reaction analysis of mRNAs for different chemokines. In addition, lymphocytes were restimulated in culture with donor antigen and supernatants assayed for different cytokines. We observed that early increases in mRNA for MCP-1 preceded a polarization to type 2 cytokine production. Infusion of NAc twice daily for 4 days following transplantation further altered chemokine mRNA expression (increased MCP-1 and RANTES; decreased CINC); led to more enhanced type 2 cytokine production relative to control animals; and further increased xenograft survival. By use of heteroantibodies to different chemokines, anti-MCP-1 alone, but not antibodies to MIP-1alpha or RANTES, abolished this early polarization in cytokine production, implying a causal link between MCP-1 production and polarization in cytokine production. We conclude that manipulation of chemokine production early after transplantation might indirectly modify graft outcome by modifying cytokine production.
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PMID:Alterations in chemokine mRNA expression in animals receiving portal vein immunization and renal allo- or xenotransplantation precede altered cytokine production. 1052 5

Leukocyte infiltration into the brain has been implicated in the development of ischemic brain damage. In this study, simulated in vitro ischemia/reperfusion and IL-1beta were found to up-regulate both the expression of intercellular adhesion molecule- (ICAM-1) in cultured human cerebromicrovascular endothelial cells (HCEC) and the adhesion of allogenic neutrophils to HCEC. Both HCEC and human fetal astrocytes (FHAS) also responded to IL-1beta and to in vitro ischemia/reperfusion by a pronounced up-regulation of IL-8 and MCP-1 mRNA and by increased release of IL-8 and MCP-1 in cell culture media. FHAS were found to release 30-times higher levels of MCP-1 than HCEC under both basal and ischemic conditions. However, 100 u/ml IL-1beta induced greater stimulation of both IL-8 and MCP-1 secretion in HCEC (50 and 20 times above controls, respectively) than in FHAS (three and two times above controls, respectively). IL-8 was the principal neutrophil chemoattractant released from IL-1beta-treated HCEC, since IL-8 antibody completely inhibited neutrophil chemotaxis enticed by HCEC media. However, the IL-8 antibody neutralized only 50% of IL-1beta-stimulated neutrophil chemoattractants released from FHAS, and 40%-60% of ischemia-stimulated chemotactic activity released by either HCEC or FHAS. These results suggest that simulated in vitro ischemia, in addition to IL-8 and MCP-1, stimulates secretion of other bioactive chemokines from HCEC and FHAS.
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PMID:Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. 1058 Jul 98


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