VCAM-1 is internalized by a clathrin-related pathway in human endothelial cells but its alpha 4 beta 1 integrin counter-receptor remains associated with the plasma membrane in human T lymphocytes

Autor: I, Ricard, M D, Payet, G, Dupuis
Rok vydání: 1998
Předmět:
Zdroj: European journal of immunology. 28(5)
ISSN: 0014-2980
Popis: Lymphocyte extravasation involves a step(s) of de-adhesion to allow trans- and subendothelial migration in response to inflammatory signals. We show here that ligated VCAM-1 was rapidly internalized (t1/2 14.5 min) in ECV 304 endothelial cells and in TNF-alpha-primed human umbilical vein-derived endothelial cells (t1/2 11.2 min). The process required energy (ATP), intracellular Ca2+, an intact cytoskeletal network and active protein kinases. The internalization of VCAM-1 involved a clathrin-dependent pathway based on the observations that 1) it was inhibited in cells treated with lysosomotropic agents or with a hypertonic concentration of sucrose, and 2) internalized VCAM-1 colocalized with clathrin. In contrast, the cross-linked alpha 4 beta 1 integrin counter-receptor of VCAM-1 remained associated with the plasma membrane of purified peripheral T and Jurkat cells. Our results suggest a model where VCAM-1 would initially participate in the retention of T cells to the endothelium by binding alpha 4 beta 1 integrin. Lymphocyte de-adhesion would be facilitated as a result of the internalization of VCAM-1. The persistent cell surface expression of alpha 4 beta 1 integrin would allow the migrating T cells to interact with and receive signal(s) from its fibronectin ligand of the extracellular matrix.
Databáze: OpenAIRE
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