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.

Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats

“…Intestinal injury induced by IR is thought to result from intestine-derived TNF-a. Moreover, TNF-a could upregulate neutrophil adhesion molecules in the intestine, particularly ICAM-1, which then plays a vital role in the influx of neutrophils in intestinal tissue [28,29] . In this study, intestinal IR induced TNF-a production, as observed as increased TNF-a levels, which were significantly reduced by intestinal IP.…”

Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression

“…45 and 46), inducible nitric oxide synthase (iNOS; see Refs. 38 and 44), and cell adhesion molecules (34,35,54). The expression of these inflammatory mediator genes is controlled, in part, by nuclear factor-B (NF-B).…”

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

“…The serum TNF-α and ICAM-1 levels can be regarded as markers for the systemic inflammatory response as they indirectly reflect the whole body production of both TNF-α and ICAM-1 in various organs [38][39][40][41] . The expression of adhesion molecules can be induced by TNF-α [38] .…”