Premium
HS1 is required for neutrophil polarization, LFA‐1 activation and leukocyte recruitment
Author(s) -
Schnoor Michael,
Logermann Silke Maria,
Jing Ding,
Li Hang,
Butz Stefan,
Vestweber Dietmar
Publication year - 2012
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.26.1_supplement.55.1
Subject(s) - leukocyte extravasation , microbiology and biotechnology , extravasation , chemotaxis , cytoskeleton , pseudopodia , cell adhesion molecule , integrin , cell adhesion , cortactin , lymphocyte function associated antigen 1 , biology , actin , adhesion , immunology , chemistry , intercellular adhesion molecule 1 , cell , receptor , biochemistry , organic chemistry
Neutrophil extravasation is a critical step in innate immunity in response to tissue injury or invading pathogens. The interaction of neutrophils with the endothelium requires activation of adhesion molecules such as the β2‐integrin LFA‐1 leading to firm adhesion, polarization and intraluminal crawling to the actual site of diapedesis. These steps require coordinated cytoskeletal remodeling. The cortactin homologue in leukocytes, hematopoietic cell‐specific lyn substrate (HS1) is an actin‐binding protein that regulates actin dynamics and may thus be relevant in the regulation of leukocyte extravasation. Indeed, we found that leukocyte adhesion and extravasation in the TNF‐α‐stimulated cremaster were strongly inhibited. This was accompanied by an increased rolling velocity pointing to the fact that the transition from rolling to firm adhesion is disturbed in the absence of HS1. This could be explained by impaired LFA‐1 activation and disturbed pseudopod formation in response to TNF‐α as revealed by electron microscopy. Importantly, we unraveled a novel signaling complex containing HS1 that is involved in the regulation of LFA‐1 activation upon inflammatory stimuli. Our results are the first physiological evidence that HS1 is crucial for orchestrating molecular events in neutrophils to mediate firm adhesion and leukocyte recruitment in vivo.