Endothelial chemokines destabilize L-selectin-mediated lymphocyte rolling without inducing selectin shedding.
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.
Grabovsky
Valentin
V
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Dwir
Oren
O
Alon
Ronen
R
D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology*
D018925:Chemokines; D019041:L-Selectin; D019204:GTP-Binding Proteins