2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      CD26/dipeptidylpeptidase IV—chemokine interactions: double‐edged regulation of inflammation and tumor biology

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      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

          Review of how chemokine processing by CD26/DPP IV regulates leukocyte trafficking.

          Abstract

          Post‐translational modification of chemokines is an essential regulatory mechanism to enhance or dampen the inflammatory response. CD26/dipeptidylpeptidase IV, ubiquitously expressed in tissues and blood, removes NH 2‐terminal dipeptides from proteins with a penultimate Pro or Ala. A large number of human chemokines, including CXCL2, CXCL6, CXCL9, CXCL10, CXCL11, CXCL12, CCL3L1, CCL4, CCL5, CCL11, CCL14, and CCL22, are cleaved by CD26; however, the efficiency is clearly influenced by the amino acids surrounding the cleavage site and although not yet proven, potentially affected by the chemokine concentration and interactions with third molecules. NH 2‐terminal cleavage of chemokines by CD26 has prominent effects on their receptor binding, signaling, and hence, in vitro and in vivo biologic activities. However, rather than having a similar result, the outcome of NH 2‐terminal truncation is highly diverse. Either no difference in activity or drastic alterations in receptor recognition/specificity and hence, chemotactic activity are observed. Analogously, chemokine‐dependent inhibition of HIV infection is enhanced (for CCL3L1 and CCL5) or decreased (for CXCL12) by CD26 cleavage. The occurrence of CD26‐processed chemokine isoforms in plasma underscores the importance of the in vitro‐observed CD26 cleavages. Through modulation of chemokine activity, CD26 regulates leukocyte/tumor cell migration and progenitor cell release from the bone marrow, as shown by use of mice treated with CD26 inhibitors or CD26 knockout mice. As chemokine processing by CD26 has a significant impact on physiologic and pathologic processes, application of CD26 inhibitors to affect chemokine function is currently explored, e.g., as add‐on therapy in viral infection and cancer.

          Related collections

          Most cited references129

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

          International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.

          Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145-176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.

            Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor.

              A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated "fusin," is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and HIV-1 infection. Antibodies to fusin blocked cell fusion and infection with normal CD4-positive human target cells. Fusin messenger RNA levels correlated with HIV-1 permissiveness in diverse human cell types. Fusin acted preferentially for T cell line-tropic isolates, in comparison to its activity with macrophagetropic HIV-1 isolates.
                Bookmark

                Author and article information

                Contributors
                jo.vandamme@rega.kuleuven.be
                Journal
                J Leukoc Biol
                J. Leukoc. Biol
                10.1002/(ISSN)1938-3673
                JLB
                Journal of Leukocyte Biology
                John Wiley and Sons Inc. (Hoboken )
                0741-5400
                1938-3673
                07 January 2016
                June 2016
                : 99
                : 6 ( doiID: 10.1002/jlb.2016.99.issue-6 )
                : 955-969
                Affiliations
                [ 1 ]KU Leuven University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, Leuven, Belgium
                Author notes
                [*] [* ]Correspondence: Laboratory of Molecular Immunology, Rega Institute for Medical Research, Dept. of Microbiology and Immunology, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. E‐mail: jo.vandamme@ 123456rega.kuleuven.be
                Article
                JLB0955
                10.1189/jlb.3MR0915-401R
                7166560
                26744452
                2878b958-9c3a-4b8b-b553-25a6435d61fa
                © 2016 Society for Leukocyte Biology

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 04 September 2015
                : 01 December 2015
                : 04 December 2015
                Page count
                Figures: 3, Tables: 0, References: 145, Pages: 15, Words: 13437
                Funding
                Funded by: Interuniversity Attraction Poles Programme
                Funded by: Belgian Science Policy Office , open-funder-registry 10.13039/501100002749;
                Funded by: I.A.P.
                Award ID: 7/40
                Funded by: Fund for Scientific Research of Flanders
                Funded by: FWO‐Vlaanderen
                Award ID: G.0764.14
                Award ID: G.0773.13
                Award ID: G.0D66.13
                Funded by: Regional Government of Flanders
                Award ID: GOA/12/017
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                June 2016
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Hematology
                post‐translational modification,leukocyte,protease,chemotaxis
                Hematology
                post‐translational modification, leukocyte, protease, chemotaxis

                Comments

                Comment on this article