Soluble ICAM-1 reduces leukocyte adhesion to vascular endothelium in ischemia-reperfusion injury in mice.
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.
Kusterer
K
K
Department of Medicine I, Johann Wolfgang Goethe University, D-60590 Frankfurt, Germany.
Bojunga
J
J
Enghofer
M
M
Heidenthal
E
E
Usadel
K H
KH
Kolb
H
H
Martin
S
S
D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001783:Blood Flow Velocity; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology* / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008642:Mesenteric Veins; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*
D000925:Anticoagulants; D011134:Polysaccharides; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; C007789:fucoidan