title: Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease.
abstract: Infection or sterile inflammation triggers site-specific attraction of leukocytes. Leukocyte recruitment is a process comprising several steps orchestrated by adhesion molecules, chemokines, cytokines and endogenous regulatory molecules. Distinct adhesive interactions between endothelial cells and leukocytes and signaling mechanisms contribute to the temporal and spatial fine-tuning of the leukocyte adhesion cascade. Central players in the leukocyte adhesion cascade include the leukocyte adhesion receptors of the β2-integrin family, such as the αLβ2 and αMβ2 integrins, or of the β1-integrin family, such as the α4β1-integrin. Given the central involvement of leukocyte recruitment in different inflammatory and autoimmune diseases, the leukocyte adhesion cascade in general, and leukocyte integrins in particular, represent key therapeutic targets. In this context, the present review focuses on the role of leukocyte integrins in the leukocyte adhesion cascade. Experimental evidence that has implicated leukocyte integrins as targets in animal models of inflammatory disorders, such as experimental autoimmune encephalomyelitis, psoriasis, inflammatory bone loss and inflammatory bowel disease as well as preclinical and clinical therapeutic applications of antibodies that target leukocyte integrins in various inflammatory disorders are presented. Finally, we review recent findings on endogenous inhibitors that modify leukocyte integrin function, which could emerge as promising therapeutic targets.
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Vasileia I
authors.initials: VI
authors.lastname: Alexaki
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kourtzelis
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Ziogas
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D016023:Integrins
keywords: Del-1; Efalizumab; Integrin; Leukocyte adhesion; Natalizumab; Vedolizumab