[PDF][PDF] Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin

Z Shulman, V Shinder, E Klein, V Grabovsky, O Yeger… - Immunity, 2009 - cell.com
Z Shulman, V Shinder, E Klein, V Grabovsky, O Yeger, E Geron, A Montresor…
Immunity, 2009cell.com
Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and
transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte
integrins to support shear-resistant motility on and across cytokine-stimulated endothelial
barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling
on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and
adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes …
Summary
Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites.
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