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Outside‐in signaling via LFA‐1 in acute inflammation
Author(s) -
Dixit Neha,
Tsuzuki Yuki,
Simon Scott I.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.17
Subject(s) - microbiology and biotechnology , integrin , chemistry , cytoskeleton , jurkat cells , receptor , icam 1 , cell adhesion , signal transduction , cell adhesion molecule , biology , cell , t cell , immunology , biochemistry , immune system
Circulating neutrophils bind to ICAM‐1 upregulated on inflamed endothelium via high affinity clustered LFA‐1. This results in an outside‐in signal that recruits Src family kinases, Rap‐1 and cytoskeletal elements like Talin and F‐actin to stabilize the high affinity integrin bond with ICAM‐1. We hypothesize that dimerization of the LFA‐1 bond to ICAM‐1 provides a critical submicron configuration to elicit outside‐in signaling critical for rearrangement of cytoskeletal components leading to directed polarization and migration of the neutrophil. Real time imaging of neutrophils rolling and arresting on recombinant ICAM‐1 and E‐selectin elicited colocalization of Rap‐1, Talin and high affinity LFA‐1 upon arrest only on dimeric and not on monomeric ICAM‐1. Calcium flux mediated by ligand induced arrest was markedly higher in neutrophils bound to dimeric ICAM‐1 as compared to the monomer. We conclude that integrin mediated outside‐in signal is dependent on the valency of the LFA‐1/ICAM‐1 bond thereby providing a key gate keeping mechanism necessary for subsequent and efficient cell polarization and transmigration. This work was supported by AI47294 to S.I.S.