Expression of adhesion molecules is specific and time-dependent in cytokine-stimulated endothelial cells in culture

Abstract

The time course of expression of the adhesion molecules E-selectin, VCAM-1, ICAM-1 and PECAM-1 was studied in interleukin-1 beta-stimulated human umbilical vein cells (HUVEC) and the subcellular sites of synthesis were determined by means of fluorescence immunohistochemistry. The maximal number of cells labelled for E-selectin was observed at 2-4 h, for VCAM-1 at 4-8 h and ICAM-1 at 6-72 h. At 8 h, E-selectin and VCAM-1 started to disappear, but ICAM-1-positive cells persisted. PECAM-1 was constitutively expressed. De novo synthesis for E-selectin started at 1 h and for both, VCAM-1 and ICAM-1 at 1.5-2 h. Maximal synthetic activity was observed at 2.5-4 h for E-selectin and at 4-6 h for VCAM-1 and ICAM-1; thereafter, synthesis slowly decreased. Transport granules occurred at 1.5 h for E-selectin and 4 h for VCAM-1; they were absent for ICAM-1. Diffuse cellular and membrane labelling indicative of the functional activity of the adhesion molecules began at 2-4 h for E-selectin, and 4 h for VCAM, but was constitutively present for ICAM-1. In conclusion, each adhesion molecule shows a specific time-dependent course of appearance and disappearance in interleukin-1 beta-stimulated HUVECs in accordance with their physiological role in vivo. These morphological results confirm data obtained by flow cytometry and Western blotting, but they provide new information about the behaviour of individual cells with regard to the sites of synthesis and cellular localization of the adhesion molecules.

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

“…It is well known that ICAM-1 and VCAM-1 are markedly upregulated on endothelial cells by the proinflammatory cytokines TNF-␣ and IL-1␤, respectively (30,31), and that HUVEC and microvascular endothelial cells are able to secrete a variety of cytokines (32). Therefore, we hypothesized that RSV-induced expression of ICAM-1 and VCAM-1 is partly mediated by an autocrine mechanism as it was reported for A549 epithelial cells (33).…”

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.…”

Cytophagic Histiocytic Panniculitis -What is the Best Therapy?

“…These cytokines may directly suppress the hematopoiesis and may activate the histiocytes and monocytes, and subsequently induce the severe cytopenia because of prominent hemophagocytosis in the bone marrow, spleen, liver and lymph nodes. In addition, cytokine-activated monocytes and vascular endothelial cells may produce the procoagulant substance (tissue factor), plasminogen activator inhibitor-1 and von Willebrand factor (7), and also adherent molecules in the cell surface (8). These molecules may lead to hypercoagulation state and organ failure.…”