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Updated: Aug 9, 2026

Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
Published on: February 11, 2009
Endothelial chemokines destabilize L-selectin-mediated lymphocyte rolling without inducing selectin shedding
Valentin Grabovsky1, Oren Dwir, Ronen Alon
1Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
Chemokines presented on specialized endothelial surfaces rapidly up-regulate leukocyte integrin avidity and firm arrest through G(i)-protein signaling. Here we describe a novel, G-protein-independent, down-regulatory activity of apical endothelial chemokines in destabilizing L-selectin-mediated leukocyte rolling. Unexpectedly, this anti-adhesive chemokine suppression of rolling does not involve L-selectin shedding. Destabilization of rolling is induced only by immobilized chemokines juxtaposed to L-selectin ligands and is an energy-dependent process. Chemokines are found to interfere with a subsecond stabilization of selectin tethers necessary for persistent rolling. This is a first indication that endothelial chemokines can attenuate in situ L-selectin adhesion to endothelial ligands at subsecond contacts. This negative feedback mechanism may underlie the jerky nature of rolling mediated by L-selectin in vivo.
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