17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biology and structure of leukocyte β 2 integrins and their role in inflammation

      review-article
      a , 1
      F1000Research
      F1000Research
      inflammation, integrins, leukocytes, integrin structure

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Integrins comprise a large family of αβ heterodimeric cell adhesion receptors that are expressed on all cells except red blood cells and that play essential roles in the regulation of cell growth and function. The leukocyte integrins, which include members of the β 1, β 2, β 3, and β 7 integrin family, are critical for innate and adaptive immune responses but also can contribute to many inflammatory and autoimmune diseases when dysregulated. This review focuses on the β 2 integrins, the principal integrins expressed on leukocytes. We review their discovery and role in host defense, the structural basis for their ligand recognition and activation, and their potential as therapeutic targets.

          Related collections

          Most cited references118

          • Record: found
          • Abstract: found
          • Article: not found

          Of mice and not men: differences between mouse and human immunology.

          Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. However, as 65 million years of evolution might suggest, there are significant differences. Here we outline known discrepancies in both innate and adaptive immunity, including: balance of leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK inhibitory receptor families Ly49 and KIR, FcR, Ig subsets, the B cell (BLNK, Btk, and lambda5) and T cell (ZAP70 and common gamma-chain) signaling pathway components, Thy-1, gammadelta T cells, cytokines and cytokine receptors, Th1/Th2 differentiation, costimulatory molecule expression and function, Ag-presenting function of endothelial cells, and chemokine and chemokine receptor expression. We also provide examples, such as multiple sclerosis and delayed-type hypersensitivity, where complex multicomponent processes differ. Such differences should be taken into account when using mice as preclinical models of human disease.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Integrin ligands at a glance.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand.

              The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.
                Bookmark

                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                4 October 2016
                2016
                : 5
                : F1000 Faculty Rev-2433
                Affiliations
                [1 ]Leukocyte Biology & Inflammation Program, Structural Biology Program, Nephrology, Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
                Author notes

                Competing interests: The author declares that he has no competing interests.

                Article
                10.12688/f1000research.9415.1
                5054827
                27781085
                53a931ad-b82b-4553-8ea6-10d28f83329f
                Copyright: © 2016 Arnaout MA

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2016
                Funding
                Funded by: National Institutes of Health
                Award ID: DK088327
                Award ID: DK48549
                Funded by: National Institutes of Diabetes, Digestive and Kidney Diseases
                Award ID: DK007540
                The author's work presented in this review was supported by National Institutes of Health grants DK088327, DK48549, and DK007540 from the National Institutes of Diabetes, Digestive and Kidney Diseases.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles
                Biomacromolecule-Ligand Interactions
                Cell Adhesion
                Cell Signaling
                Cell Signaling & Trafficking Structures
                Drug Discovery & Design
                Genetics of the Immune System
                Immune Response
                Immunity to Infections
                Immunopharmacology & Hematologic Pharmacology
                Leukocyte Signaling & Gene Expression
                Membrane Proteins & Energy Transduction
                Molecular Pharmacology

                inflammation,integrins,leukocytes,integrin structure
                inflammation, integrins, leukocytes, integrin structure

                Comments

                Comment on this article