title: The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats.
abstract: Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17-45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.
authors.affiliation: Department of Anesthesiology, Lund University Hospital, Sweden.
authors.forename: Knut
authors.initials: K
authors.lastname: Olanders
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Sun
authors.forename: Anna
authors.initials: A
authors.lastname: Börjesson
authors.forename: Marwan
authors.initials: M
authors.lastname: Dib
authors.forename: Ellen
authors.initials: E
authors.lastname: Andersson
authors.forename: Ake
authors.initials: A
authors.lastname: Lasson
authors.forename: Tomas
authors.initials: T
authors.lastname: Ohlsson
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D004730:Endothelium, Vascular / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008967:Molecular Biology / Q000379:methods; D009504:Neutrophils / Q000502:physiology*; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000418:Albumins; D000911:Antibodies, Monoclonal; D011480:Protease Inhibitors; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase