Effects of Cytokines on the Expression of Cell Adhesion Molecules by Cultured Human Omental Mesothelial Cells

Abstract

Cultured mesothelial cells (HOMES) are very responsive to the proinflammatory cytokines, interleukin (IL)-l and tumor necrosis factor-α (TNF-α). E-selectin, ICAM-1 and VCAM-1 are known to play an important role, because they are presented by diverse cell types, for example endothelial cells (ECs), and interact with coresponding ligands on white blood cell membranes. In this study, the expression of ICAM-1, VCAM-1, E-selectin as well as PECAM-1 on cultured HOMES was studied over 5,24,48 and 72 h exposure to IL-1 β, interferon-γ and TNF-α. In previous studies we have shown that IL-l β and TNF-α increase the expression of ICAM-1, E-selectin and VCAM-1 on the cytoplasmatic membranes of HUVECs, HSVECs and HAFECs (ECs from human umbilical vein, saphenous vein and femoral artery, respectively). Using a comparative quantitative cell enzyme immunoassay, we found that expression of the adhesion molecules ICAM-1 and VCAM-1 was significantly increased on HOMES in a dose- and time-dependent manner, compared to nonstimulated cells. Thus, ICAM-1 increased dramatically after 5 h incubation with TNF-α. Values of about 450% of the control level were measured. VCAM-1 was similarly stimulated after 24 h incubation with the same cytokine, although its level of expression was significantly lower than that of ICAM-1. In contrast to findings in the literature, VCAM-1 was not found to be expressed constitutively. E-selectin was neither constitutively expressed nor markedly inducible on HOMES. Only weak expression was found after 24 h incubation with high-dose IL-lβ. PEC AM-1 was expressed constitutively, as became evident in antibody dilution studies. These data indicate that HOMES respond to inflammatory stimuli, in some ways in a similar fashion to vascular endothelial cells, but also show a specific pattern of antigen presentation. The results are important for a better understanding of inflammatory processes in serous cavities. The data are also relevant for the improvement of antithrombogenous surfaces of the lumina of vascular prostheses by cell seeding.

The pathogenesis of transfusion‐related acute lung injury (TRALI)

“…2, right panel). In addition to the constitutively expressed ICAM-2, activated endothelial cells upregulate surface membrane receptors that allow neutrophil adhesion, including ligands for l-selectin (Spertini et al, 1991), p-selectin, and ICAM-1 (Gerritsen & Bloor, 1993;Klein et al, 1995;Scholz et al, 1996). Neutrophils that pass through the narrow lung capillaries may well get stuck if the endothelium is activated and ligands for l-selectin have been upregulated, as the process of retaining neutrophils within the pulmonary capillaries has been described to be selectindependent (Yamaguchi et al, 1997;Kubo et al, 1999).…”

Endothelial cell functions

“…Since L-selectin is constitutively expressed on leukocytes, the induced adherence in inflammatory situation requires induction of L-selectin ligand and/or of E-and P-selectins on the endothelial surface. E-selectin is transcriptionally induced by cytokines such as IL-1, TNF-a, or by LPS (Klein et al, 1995;Scholz et al, 1996). In contrast, P-selectin is stored in the membrane of storage granules, the WeibelPalade bodies, in endothelial cells (McEver et al, 1989).…”

“…The complementary endothelial ligand for Mac-1 is intercellular adhesion molecule-1 (ICAM-1), an Ig-like molecule that exhibits low constitutive presentation of endothelial cell membranes, but is markedly induced by exposure of endothelial cells to cytokines (Klein et al, 1995;Scholz et al, 1996). LFA-1 can also bind ICAM-1 but it has higher affinity to a related protein, ICAM-2.…”

Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum

“…Although tumour cell adhesion is the first step for successful recurrence, few studies have been performed to elucidate the mechanisms behind this process. In vitro up-regulation or de novo synthesis of cell adhesion molecules has been reported in a wide range of cell types after pretreatment with inflammatory cytokines [7][8][9][10]. These studies, however, do not predict the effect on tumour cell adhesion.…”