Inflammation-dependent α5β1 (very late antigen-5) expression on leukocytes reveals a functional role for this integrin in acute peritonitis

Journal of Leukocyte Biology

Mauro Perretti²  Doerte Vossmeyer¹  André L. F. Sampaio³  John F. Marshall²  Grit Zahn¹  Claudia Christner¹  Giovanna Leoni² 

[1] Jerini AG, Berlin, Germany; and Jerini AG, Berlin, Germany; and Jerini AG, Berlin, Germany; andBarts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom;;Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; FarManguinhos–FIOCRUZ, Rio de Janeiro, Brazil Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; FarManguinhos–FIOCRUZ, Rio de Janeiro, Brazil FarManguinhos–FIOCRUZ, Rio de Janeiro, Brazil Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; FarManguinhos–FIOCRUZ, Rio de Janeiro, Brazil

关键词: recruitment;    adhesion molecule;    VLA-5;    fibronectin;    intravital microscopy;    cell adhesion;   

DOI  :  10.1189/jlb.1009670

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The potential role of α5β1 (VLA-5) in leukocyte trafficking in zymosan-induced acute peritonitis was determined. In naïve mice, ∼98% of Gr1high cells (PMN) in bone marrow and circulation were α5β1-negative; these profiles were modestly affected by peritoneal injection of zymosan. In contrast, ∼30% of Gr1high cells recruited by zymosan (24 h) to the peritoneal cavity expressed α5β1. With respect to F4/80+ cells, ∼60% of bone marrow and peripheral blood populations expressed α5β1, with ∼90% positivity in resident cells of noninflamed peritoneum. Analysis of α5β1 expression revealed inflammation-dependent increased expression on Gr1high and F4/80+ cells in bone marrow, blood, and peritoneal cavity. Blockade of α5β1, by an anti-α5 mAb, attenuated zymosan-induced 24 h recruitment of Gr1high and F4/80+ cells. At least one underlying mechanism of this action was reduction of cell adhesion and transmigration across microvascular vessels, as revealed by intravital microscopy. Confocal analyses indicated that deposition of fibronectin, the principal ligand for α5β1, was up-regulated significantly on and around the inflamed mesenteric microvasculature. These data suggest that the effects of α5-blockade may be a result of inhibition of α5β1-dependent leukocyte adhesion to and migration along the fibronectin matrix. This is the first report that identifies a functional role for α5β1 in leukocyte trafficking during acute inflammation.

【 授权许可】

Unknown