Disease relevance of ICAM1

• 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 [1].
• The present study examines cardiac-specific lymph collected from awake dogs during 1-h coronary occlusion and 3 d of reperfusion for its ability to induce both ICAM-1 expression in cardiac myocytes, and neutrophil-myocyte adherence [2].
• METHODS AND RESULTS: In the present study, we used in situ hybridization techniques to detect ICAM-1 mRNA and examine the cells of origin, relation to cell injury, and relation to inflammatory infiltration after 1 hour of ischemia and varying times of reperfusion [3].
• CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that expression of E-selectin and ICAM-1 mRNA increased during sepsis, particularly in the lungs and liver, and that this increase was associated with neutrophil accumulation [4].
• In situ hybridization studies suggest that ICAM-1 mRNA is found in viable myocardial cells on the edge of the myocardial infarction within 1 h of reperfusion [5].

High impact information on ICAM1

• 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 [1].
• 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 [1].
• These cytokines induce synthesis and surface expression of intercellular adhesion molecule-1 (ICAM-1) on the myocyte, and neutrophil adhesion is almost entirely CD18 and ICAM-1 dependent [2].
• Reperfusion lymph induced ICAM-1 expression in isolated myocytes, and myocyte adherence to ZAS-stimulated neutrophils that was completely inhibited by anti-CD18 and anti-ICAM-1 monoclonal antibodies [2].
• We have previously shown that cytokines and postischemic cardiac lymph induce expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on canine adult cardiac myocytes [6].

Biological context of ICAM1

• Administration of a soluble TNF-alpha inhibitor reduced NFkappaB activation, ICAM-1 upregulation, and myocardial injury following ischemia-reperfusion [7].
• Blood flow (fluorescent or radioactive microspheres), ICAM-1 protein expression (immunohistochemistry), ICAM-1 gene activation (Northern blotting), and nuclear DNA-binding activity of NF kappa B and AP-1 (electrophoretic mobility shift assays) were assessed in myocardial tissue samples [8].
• In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event [9].
• The staining patterns observed with REC16-11 and REC4-1 were compared with those obtained with the MoAb anti-rat ICAM-1, which is a cell adhesion molecule in HEVs [10].

Anatomical context of ICAM1

• These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium [1].
• These results indicate that H2O2 in the absence of evidence for permanent endothelial cell injury, can induce a transient, reversible, platelet-activating factor-dependent adherence of PMNs to vessels by mechanisms that depend on an intact endothelium and involve CD18 on the PMN and ICAM-1 on the endothelium [11].
• Inflammatory leukocytes further extend the zone of chondrocyte death by adhering to chondrocytes expressing ICAM-1 and by inducing the accumulation of free oxygen radicals in the chondrocyte cytoplasm [12].
• Leukocyte-mediated killing could be blocked by desferoxamine or by antibodies to CD18, which prevent attachment of leukocytes to ICAM-1-expressing chondrocytes [12].
• ICAM-1 protein expression was high in vascular endothelium after ischemia-reperfusion but was markedly reduced by MPG [13].

Associations of ICAM1 with chemical compounds

• Hydrogen peroxide pretreatment of perfused canine vessels induces ICAM-1 and CD18-dependent neutrophil adherence [11].
• H2O2-induced PMN retention was completely inhibited by addition of catalase or the hydroxyl radical scavenger dimethylthiourea to the perfusate by incubation of the PMN with a monoclonal antibody (Mab) against CD18 (R15.7) or by perfusion of the H2O2-treated vessel with CL18/6, a Mab against canine ICAM-1 (intercellular adhesion molecule-1) [11].
• Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells [14].
• In addition, the intracellular adhesion molecule-1 (ICAM-1) level was significantly higher in the control group than in the prostacyclin group (9.26+/-2.13 in the control group and 5.13+/-1.66 ng/mL in the prostacyclin group) [15].
• Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages [14].

Analytical, diagnostic and therapeutic context of ICAM1

• Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction [16].
• ICAM-1 level was also elevated in the control group [17].
• CONCLUSIONS: Cardiopulmonary bypass resulted in intercellular adhesion molecule-1 induction in the canine lung during recovery [18].
• Immunoelectron microscopy demonstrated the pulmonary capillary endothelium capable of increased intercellular adhesion molecule-1 protein expression at the 9-hour time point [18].
• Western blots showed intercellular adhesion molecule-1 protein expression before bypass but a measurable increase in intercellular adhesion molecule-1 protein in four of seven dogs in the bypass group by the ninth hour of recovery [18].

References