Role of ICAM-1 in chronic hepatic allograft rejection in the rat

Abstract

The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10 mg · kg−1 · day−1 × 6 days ip) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital microscopy. Liver histology, biochemistry, and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared with isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared with control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3 ± 1.2 days) compared with the controls (25.2 ± 2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1 dependent and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.

Inhibition of Mammalian Target of Rapamycin Potentiates Thrombin-Induced Intercellular Adhesion Molecule-1 Expression by Accelerating and Stabilizing NF-κB Activation in Endothelial Cells

“…The data are consistent with a role of mTOR as a "speed breaker" in the pathway to NF-B activation, an essential event in the mechanism of ICAM-1 expression in endothelial cells (6,42). We provide evidence that thrombin induces activation of mTOR in endothelial cells and that inhibition of mTOR potentiates thrombin-induced ICAM-1 expression.…”

Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice

“…One of the key molecules responsible for the firm PMN adhesion to the vascular endothelium is ICAM-1 (CD54). ICAM-1 is a member of the immunoglobulin superfamily and functions as a ligand for leukocyte integrin ␣L␤2 (lymphocyte function-associated antigen-1), which mediates leukocyte adhesion in response to proinflammatory stimulus(i) imposed by cytokines, e.g., TNF-␣ and IL-1␤, or bacterial products such as LPS (14,15,35,56,68). It is also agreed that upregulation of ICAM-1 on microvascular endothelium serves as a prime marker of vascular activation and correlates with the infiltration of PMN into affected organs (11,16,45,50,52).…”

“…The mechanism(s) of PMN recruitment to the affected organs is a complex multistep process and involves series of adhesive interactions (rolling, firm adhesion, and migration) between PMN and vascular endothelial cells (15,16,19,67,68). Neutrophil sequestration has been associated with the increased chemokine production, augmented expression of the ␤ 2 -integrin CD11b/CD18 and upregulation of vascular proadhesive phenotype [e.g., increased expression of E-selectin and vascular cell adhesion molecules, such as ICAM-1 and VCAM-1 (34,17,40)].…”

Zinc Finger Protein A20 Promotes Regeneration of Small-for-Size Liver Allograft and Suppresses Rejection and Results in a Longer Survival in Recipient Rats

“…NF-B activation after partial hepatectomy is required to prevent apoptosis and allow for cell cycle progression. On the other hand, NF-B activation is also attributable to sinusoidal endothelial cells activation and expression of adhesion molecules such as ICAM-1, which mediate the recruitment of LIMCs into liver [13,27,28] and is involved in liver allograft rejection. ICAM-1 has been shown to be of particular importance for the recognition of donor cells by recipient T lymphocytes.…”