title: ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells in vivo.
abstract: Intercellular adhesion molecule 2 (ICAM-2) is expressed on endothelial cells (ECs) and supports neutrophil extravasation. However, the full details of its role remain unknown, and the present study investigates the functional mechanisms of ICAM-2 in neutrophil-endothelial-cell interactions. Our initial studies showed expression of ICAM-2 at both EC junctions and on the EC body. In line with the observed expression profile analysis of neutrophil-vessel-wall interactions using real-time in vivo confocal microscopy identified numerous functional roles for ICAM-2 within the vascular lumen and at the stage of neutrophil extravasation. Functional or genetic blockade of ICAM-2 significantly reduced neutrophil crawling velocity, increased frequency of crawling with a disrupted stop-start profile, and prolonged interaction of neutrophils with EC junctions prior to transendothelial cell migration (TEM), collectively resulting in significantly reduced extravasation. Pharmacological blockade of the leukocyte integrin MAC-1 indicated that some ICAM-2-dependent functions might be mediated through ligation of this integrin. These findings highlight novel roles for ICAM-2 in mediating luminal neutrophil crawling and the effect on subsequent levels of extravasation.
authors: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors: Krishma
authors: K
authors: Halai
authors: James
authors: J
authors: Whiteford
authors: Bin
authors: B
authors: Ma
authors: Sussan
authors: S
authors: Nourshargh
authors: Abigail
authors: A
authors: Woodfin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Extravasation; ICAM-2; Intercellular adhesion molecule 2; Intravascular crawling; Leukocyte; Neutrophil