Dynamic shifts in LFA-1 affinity regulate neutrophil rolling, arrest, and transmigration on inflamed endothelium Running Title: LFA-1 affinity regulates neutrophil recruitment
نویسندگان
چکیده
1 University of California, Davis. Department of Biomedical Engineering. Genome and Biomedical Sciences Facility, 451 E. Health Sciences Dr., Davis, California, 95616-5294. 530-752-1430 (U. S., A. F. H. L., M. R. S.) 530-754-2193 (C. E. G.), 530-752-0299 (S. I. S.). Fax 530-754-5739 2 ICOS Corporation, 22021 20 Ave. SE, Bothell, Washington 98021. 3 Current Address: The Scripps Research Institute, Department of Immunology, 10030 North Torrey Pines Road SP-231, La Jolla, CA 92037. 858-784-7753.
منابع مشابه
Dynamic shifts in LFA-1 affinity regulate neutrophil rolling, arrest, and transmigration on inflamed endothelium.
Polymorphonuclear leukocyte (PMN) recruitment to vascular endothelium during acute inflammation involves cooperation between selectins, G-proteins, and beta2-integrins. LFA-1 (CD11a/CD18) affinity correlates with specific adhesion functions because a shift from low to intermediate affinity supports rolling on ICAM-1, whereas high affinity is associated with shear-resistant leukocyte arrest. We ...
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Leukocyte capture on inflamed endothelium is facilitated by a shift in LFA-1 from low to high affinity that supports binding to ICAM-1. LFA-1 bonds help anchor polymorphonuclear leukocytes (PMN) to inflamed endothelium in shear flow, and their redistribution to the leading edge guides pseudopod formation, migration, and extravasation. These events can be disrupted at the plasma membrane by stab...
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Neutrophil arrest and migration on inflamed endothelium is dependent upon a conformational shift in CD11a/CD18 (LFA-1) from a low to high affinity and clustered state which determines the strength and lifetime of bond formation with intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal adaptor proteins kindlin-3 and talin-1 anchor clustered LFA-1 to the cytoskeleton and support the transitio...
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Lymphocyte function-associated antigen-1 (LFA-1) is a heterodimeric integrin consisting of α(L) (gene name, Itgal) and β(2) (gene name, Itgb2) subunits expressed in all leukocytes. LFA-1 is essential for neutrophil recruitment to inflamed tissue. Activation of LFA-1 by chemokines allows neutrophils and other leukocytes to undergo arrest, resulting in firm adhesion on endothelia expressing inter...
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Acute inflammation triggers the innate immune response of neutrophils that efficiently traffic from the bloodstream to concentrate at high numbers at the site of tissue infection or wounding. A gatekeeper in this process is activation of β(2) integrins, which form bond clusters with ICAM-1 on the endothelial surface. These bond clusters serve dual functions of providing adhesive strength to anc...
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