title: Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium.
abstract: Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) post-ischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.
authors.affiliation: Speros P. Martel Laboratory, Department of Pediatrics, Methodist Hospital, Houston, Texas.
authors.forename: G L
authors.initials: GL
authors.lastname: Kukielka
authors.forename: H K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: L
authors.initials: L
authors.lastname: Michael
authors.forename: A M
authors.initials: AM
authors.lastname: Manning
authors.forename: K
authors.initials: K
authors.lastname: Youker
authors.forename: C
authors.initials: C
authors.lastname: Lane
authors.forename: M L
authors.initials: ML
authors.lastname: Entman
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1; D008196:Lymph / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1