Cellular activation through the ligation of intercellular adhesion molecule-1

Clayton, Aled ORCID: https://orcid.org/0000-0002-3087-9226, Evans, Rachel A., Pettit, Elizabeth, Hallett, Maurice, Williams, John David and Steadman, Robert ORCID: https://orcid.org/0000-0002-1303-2496 1998. Cellular activation through the ligation of intercellular adhesion molecule-1. Journal of Cell Science 111 (4) , pp. 443-453.

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Abstract

In addition to its role in mediating leukocyte adherence to and migration across the endothelium, intercellular adhesion molecule (ICAM)-1 on the surface of interstitial cells has been implicated as a principal adhesion molecule controlling leukocyte infiltration at inflammatory sites. The present study demonstrates that leukocyte binding to fibroblasts isolated from both the human renal cortex and lung and to endothelial cells induced the de novo synthesis of ICAM-1 mRNA and protein through the ICAM-1-dependent activation of the cultured cells. This was mimicked by specifically cross-linking the ICAM-1 receptor with anti-ICAM-1 antibodies. Following cross-linking there was a two- to threefold increase in the steady state levels of ICAM-1 mRNA isolated from the cells. The expression of this mRNA peaked at 1–3 hours and was dose-dependent on the concentration of secondary cross-linking antibody. Peak protein expression was between 18 and 48 hours after cross-linking. Additional data demonstrated a similar increase in the expression of VCAM-1 following ICAM-1 cross-linking. In contrast, there was no reponse as a result of incubation with an isotype-matched control antibody. Both the binding of leukocytes and the cross-linking of ICAM-1 triggered a rise in cytosolic free calcium as the result, in part, of a calcium influx from the extracellular medium. Using BAPTA-AM to chelate intracellular calcium ions indicated that this increase in cytosolic free calcium was directly involved in the initiation of adhesion molecule upregulation. The present study demonstrates that both endothelial cells and fibroblasts can be stimulated by the direct cell surface interaction of ICAM-1 with its ligands on inflammatory cells. One phenotypic change resulting from this interaction is the upregulated synthesis and expression of more cellular adhesion molecules. This may have profound implications for the control and persistence of a leukocyte infiltrate and the progression of inflammatory disease. © 1998 by Company of Biologists

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	The Company of Biologists Ltd
ISSN:	0021-9533
Last Modified:	25 Oct 2022 10:03
URI:	https://orca.cardiff.ac.uk/id/eprint/60990

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