Chemokines Trigger Immediate β2 Integrin Affinity and Mobility Changes
2000; Cell Press; Volume: 13; Issue: 6 Linguagem: Inglês
10.1016/s1074-7613(00)00074-1
ISSN1097-4180
AutoresGabriela Constantin, Muhammad Zeeshan Majeed, Cinzia Giagulli, Laura Piccio, Ji Yun Kim, Eugene C. Butcher, Carlo Laudanna,
Tópico(s)T-cell and B-cell Immunology
ResumoChemokines trigger rapid integrin-dependent lymphocyte arrest to vascular endothelium. We show that the chemokines SLC, ELC, and SDF-1α rapidly induce lateral mobility and transient increase of affinity of the β2 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.
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