Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow.
Chemokines trigger rapid integrin-dependent lymphocyte arrest to vascular endothelium. We show that the chemokines SLC, ELC, and SDF-1alpha rapidly induce lateral mobility and transient increase of affinity of the beta2 integrin LFA-1. Inhibition of phosphatidylinositol 3-OH kinase (PI(3)K) activity blocks mobility but not affinity changes and prevents lymphocyte adhesion to ICAM-1 immobilized at low but not high densities, suggesting that mobility enhances the frequency of encounters between high-affinity integrin and ligand but that at higher ligand density affinity changes are sufficient for arrest. Thus, chemokines trigger, through distinct signaling pathways, both a high-affinity state and lateral mobility of LFA-1 that can coordinately determine the vascular arrest of circulating lymphocytes under physiologic conditions.
Constantin
G
G
Department of Pathology, Faculty of Medicine, University of Verona, Italy.
Majeed
M
M
Giagulli
C
C
Piccio
L
L
Kim
J Y
JY
Butcher
E C
EC
Laudanna
C
C
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism* / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010581:Peyer's Patches / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D013997:Time Factors
C515460:CCL19 protein, human; C515478:CCL21 protein, human; D018821:CD18 Antigens; C515255:CXCL12 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D010450:Endopeptidases