Soluble ICAM-1 reduces leukocyte adhesion to vascular endothelium in ischemia-reperfusion injury in mice

1998 ◽  
Vol 275 (2) ◽  
pp. G377-G380 ◽  
Author(s):  
Klaus Kusterer ◽  
Jörg Bojunga ◽  
Michael Enghofer ◽  
Edmund Heidenthal ◽  
Klaus H. Usadel ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Leukocyte Adherence ◽  
Intercellular Adhesion Molecule 1 ◽  
Reperfusion Period

Ischemia-reperfusion injury is a pathogenic factor in the course of many clinical disorders, such as myocardial infarction, stroke, organ transplantation, burns, and circulatory shock. The extent of ischemia-reperfusion injury is dependent on the number of infiltrating leukocytes. With in vivo microscopy, we evaluated the effect of the recombinant form of soluble murine intercellular adhesion molecule-1 (ICAM-1) on ischemia-reperfusion injury in an animal model. A mesenteric vein was occluded with a clamp for 45 min. During a reperfusion period of 30 min, the number of leukocytes rolling along the endothelium and the number of adherent leukocytes were measured with and without pretreatment with recombinant ICAM-1. The number of leukocytes rolling along the endothelial surface increased more than twofold during postischemic perfusion ( P < 0.05). Recombinant ICAM-1 had no effect on leukocyte rolling. In the control group, firm adherence of leukocytes was increased 10-fold. Recombinant ICAM-1 dose dependently reduced firm adhesion to the endothelium in response to prior ischemia. After 30 min, reperfusion pretreatment with recombinant ICAM-1 inhibited leukocyte adherence from 512 ± 123 to 166 ± 34 leukocytes/mm2( P < 0.01). We demonstrate here for the first time that soluble recombinant ICAM-1 is able to reduce leukocyte adherence to mesenteric venules in postischemic reperfusion injury dose dependently. Because soluble ICAM-1 is naturally circulating in human serum, the therapeutic use of soluble recombinant forms of ICAM-1 may represent a physiological way to protect against ischemiareperfusion injury.

L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver

1998 ◽  
Vol 275 (6) ◽  
pp. G1341-G1352 ◽  
Author(s):  
Surinder S. Yadav ◽  
David N. Howell ◽  
Wenshi Gao ◽  
Douglas A. Steeber ◽  
Robert C. Harland ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Mutant Mice ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin −/−, ICAM-1 −/−, and L-selectin/ICAM-1 −/−) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L-selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L-selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.

Role of Mac-1 and ICAM-1 in ischemia-reperfusion injury in a microcirculation model of BALB/C mice

1994 ◽  
Vol 267 (4) ◽  
pp. H1320-H1328 ◽  
Author(s):  
D. Nolte ◽  
R. Hecht ◽  
P. Schmid ◽  
A. Botzlar ◽  
M. D. Menger ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Fluorescein Isothiocyanate ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Capillary Perfusion ◽  
Inflammatory Reactions

The leukocyte beta 2-integrin Mac-1 (CD11b/CD18) and its endothelial ligand intercellular adhesion molecule 1 (ICAM-1) are involved in leukocyte adhesion to and macromolecular leakage from postcapillary venules during inflammatory reactions. Both events are also encountered after ischemia-reperfusion of striated muscle, suggesting a central role of both adhesion proteins in reperfusion injury. Using intravital fluorescence microscopy and a microcirculation model in awake BALB/C mice, we investigated the effects of monoclonal antibodies (MAb) and Fab fragments to Mac-1 and MAb to ICAM-1 on leukocyte-endothelium interaction and macromolecular leakage of fluorescein isothiocyanate-dextran (1.5 x 10(5) mol wt) in striated skin muscle after 3 h of ischemia followed by reperfusion. We demonstrated that administration of MAb and Fab to Mac-1 before reperfusion was as effective as administration of MAb to ICAM-1, which was found to be significantly upregulated in the postischemic tissue by immunohistochemical analysis, in preventing postischemic leukocyte adhesion to and macromolecular leakage from postcapillary venules, whereas postischemic leukocyte rolling was not affected after MAb administration. Postischemic capillary perfusion was efficiently preserved in animals treated with anti-Mac-1 and anti-ICAM-1 MAb compared with animals receiving the isotype-matched control antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective Effect of Shen-Fu on Myocardial Ischemia-Reperfusion Injury in Rats

2004 ◽  
Vol 32 (02) ◽  
pp. 209-220 ◽  
Author(s):  
Shu-Yun Zheng ◽  
Jie Sun ◽  
Xin Zhao ◽  
Jian-Guo Xu
Keyword(s):  
Reperfusion Injury ◽  
Hydroxyl Radicals ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Control Group ◽  
Sod Activity ◽  
Reperfusion Period ◽  
Myocardial Ischemia Reperfusion

The present study used in vivo rat heart to investigate (1) whether Shen-Fu (SF), a traditional Chinese formulation comprising Radix Ginseng (RG) and Radix Aconitum Carmichaeli (AC), is protective against myocardium damage due to ischemia-reperfusion injury, and (2) whether the cardioprotective effect of SF is related to scavenging of hydroxyl radicals. The model of ischemia-reperfusion injury was established by ligation of left anterior descending coronary artery for 60 minutes followed by reperfusion for 240 minutes in anesthetized rats. The size of infarction and the pathologic changes of myocardium were observed. Lactate dehydrogenase (LDH) and creatine kinase (CK) in serum, the amounts of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were measured at the end of the reperfusion period. Pretreatment groups with SF (10 mg/kg), RG (9 mg/kg) and AC (1 mg/kg) inhibited the rise in MDA and LDH as well as CK, increased SOD activity, reduced the size of infarction, and improved the pathologic changes of myocardium during ischemia-reperfusion compared with the control group. The effect of SF is better than that of RG and AC. These results indicate that SF, RG and AC protect obviously myocardium against damage due to ischemia-reperfusion in rats. The cardioprotective effect of SF injection may be in part related to scavenging of hydroxyl radicals or inhibition of lipid peroxidation. SF is more effective than its separated herbal extracts prepared from RG and AC.

Cardioprotective effect of rosuvastatin in vivo is dependent on inhibition of geranylgeranyl pyrophosphate and altered RhoA membrane translocation

2007 ◽  
Vol 292 (6) ◽  
pp. H3158-H3163 ◽  
Author(s):  
Aliaksandr Bulhak ◽  
Joy Roy ◽  
Ulf Hedin ◽  
Per-Ove Sjöquist ◽  
John Pernow
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Control Group ◽  
Geranylgeranyl Pyrophosphate ◽  
Rhoa Protein ◽  
Coa Reductase

Hydroxymethyl glutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) protect the myocardium against ischemia-reperfusion injury via a mechanism unrelated to cholesterol lowering. Statins may inhibit isoprenylation and thereby prevent activation of proteins such as RhoA. We hypothesized that statins protect the myocardium against ischemia-reperfusion injury via a mechanism involving inhibition of geranylgeranyl pyrophosphate synthesis and translocation of RhoA to the plasma membrane. Sprague-Dawley rats were given either the HMG-CoA reductase inhibitor rosuvastatin, geranylgeranyl pyrophosphate dissolved in methanol, the combination of rosuvastatin and geranylgeranyl pyrophosphate, rosuvastatin and methanol, or distilled water (control) by intraperitoneal injection for 48 h before ischemia-reperfusion. Animals were anesthetized and either subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion whereat infarct size was determined, or the expression of RhoA protein was determined in cytosolic and membrane fractions of nonischemic myocardium. There were no significant differences in hemodynamics between the control group and the other groups before ischemia or during ischemia and reperfusion. The infarct size was 80 ± 3% of the area at risk in the control group. Rosuvastatin reduced infarct size to 64 ± 2% ( P < 0.001 vs. control). Addition of geranylgeranyl pyrophosphate (77 ± 2%, P < 0.01 vs. rosuvastatin) but not methanol (65 ± 2%, not significant vs. rosuvastatin) abolished the cardioprotective effect of rosuvastatin. Geranylgeranyl pyrophosphate alone did not affect infarct size per se (84 ± 2%). Rosuvastatin increased the cytosol-to-membrane ratio of RhoA protein in the myocardium ( P < 0.05 vs. control). These changes were abolished by addition of geranylgeranyl pyrophosphate. We conclude that the cardioprotection and the increase of the RhoA cytosol-to-membrane ratio induced by rosuvastatin in vivo are blocked by geranylgeranyl pyrophosphate. The inhibition of geranylgeranyl pyrophosphate formation and subsequent modulation of cytosol/membrane-bound RhoA are of importance for the protective effect of statins against myocardial ischemia-reperfusion injury.

Effects of NF-κB inhibition on mesenteric ischemia-reperfusion injury

2003 ◽  
Vol 284 (4) ◽  
pp. G713-G721 ◽  
Author(s):  
Lei Zou ◽  
Bashir Attuwaybi ◽  
Bruce C. Kone
Keyword(s):  
Reperfusion Injury ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Interleukin 6 ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-κB (NF-κB) has been implicated in this process, we treated rats with vehicle or the IκB-α 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-κB 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 IκB-α phosphorylation at Ser32,Ser36 was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IκB-α was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas α-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IκB-α. Thus NF-κB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.

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