+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases


      Read this article at

          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.


          Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology.

          Related collections

          Most cited references124

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

          Eosinophils: changing perspectives in health and disease

          Key Points Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have provided a more sophisticated understanding of eosinophil effector functions and a more nuanced view of their contributions to the pathogenesis of various diseases, including asthma and respiratory allergies, eosinophilic gastrointestinal diseases, hypereosinophilic syndromes and parasitic infection. Eosinophils are granulocytes that develop in the bone marrow from pluripotent progenitors in response to cytokines, such as interleukin-5 (IL-5), IL-3 and granulocyte–macrophage colony-stimulating factor (GM-CSF). Mature eosinophils are released into the peripheral blood and enter tissues in response to cooperative signalling between IL-5 and eotaxin family chemokines. Eosinophils in peripheral blood and tissues are uniquely identified by their bilobed nuclei, their large specific granules that store cytokines, cationic proteins and enzymes, and their expression of the IL-5 receptor and CC-chemokine receptor 3 (CCR3). In addition, the receptors sialic acid-binding immunoglobulin-like lectin 8 (SIGLEC-8) and SIGLEC-F are expressed by human and mouse eosinophils, respectively. IL-5 has a central and profound role in all aspects of eosinophil development, activation and survival. IL-5 is produced by T helper 2 (TH2) cells, and more recently the contributions of the epithelium-derived innate cytokines thymic stromal lymphopoietin (TSLP), IL-25 and IL-33 in promoting eosinophilia via the induction of IL-5 have also been recognized. Although eosinophil responses are influenced by cytokines produced by T cells, eosinophils in turn modulate the functions of B and T cells. Eosinophils also communicate with a range of innate immune cells (such as mast cells, dendritic cells, macrophages and neutrophils). Eosinophils serve to bridge innate and adaptive immunity by regulating the production of chemoattractants and cytokines (including CC-chemokine ligand 17 (CCL17), CCL22, a proliferation-inducing ligand (APRIL) and IL-6) and via antigen presentation. Both successful and unsuccessful attempts to target eosinophils have yielded remarkable insights into their contribution to disease pathogenesis. Many eosinophil-associated inflammatory conditions have been shown to be heterogeneous in nature. As such, successful therapeutic strategies will depend on the correlation of disease activity with dysregulated eosinophil function as well as the identification of the crucial molecules that regulate eosinophil accumulation in the affected tissues. Supplementary information The online version of this article (doi:10.1038/nri3341) contains supplementary material, which is available to authorized users.
            • Record: found
            • Abstract: found
            • Article: not found

            Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

            Eosinophil-derived neurotoxin (EDN) is an eosinophil granule–derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2–myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specific Th2 immune responses.
              • Record: found
              • Abstract: found
              • Article: not found

              Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo.

              Activated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, C1 esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking C1 esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

                Author and article information

                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                BioMed Central (London )
                11 February 2016
                11 February 2016
                : 9
                : 7
                [ ]Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA
                [ ]Division of Allergy, Department of Pediatrics, Nippon Medical School, Tokyo, Japan
                [ ]Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois, Chicago, IL USA
                [ ]Harvard Medical School, Brigham and Women’s Hospital, Boston, MA USA
                [ ]Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT USA
                [ ]The School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
                [ ]Department of Dermatology, University of Utah, School of Medicine, Salt Lake City, UT USA
                [ ]Virginia Commonwealth University, Children’s Hospital of Richmond, Richmond, VA USA
                [ ]Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI USA
                [ ]Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD USA
                [ ]University of Utah, Salt Lake City, UT USA
                [ ]The Hebrew University of Jerusalem, Jerusalem, Israel
                [ ]Clinical Immunology and Allergy, Department of Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
                [ ]Allergy and Immunology Group, Research Institute of Medical Science, Nihon University Graduate School of Medicine, Tokyo, Japan
                [ ]Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA
                [ ]Virginia Commonwealth University, Richmond, VA USA
                [ ]University of Bern, Institute of Pharmacology, Bern, Switzerland
                [ ]Southampton General Hospital, Immunopharmacology Group, Southampton, Hampshire UK
                [ ]Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy
                © Metcalfe et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                : 3 November 2015
                : 14 January 2016
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R21HL118588
                Award ID: P01 HL088594
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Funded by: FundRef http://dx.doi.org/10.13039/100000038, U.S. Food and Drug Administration;
                Award ID: R01FD004086
                Award Recipient :
                Custom metadata
                © The Author(s) 2016



                Comment on this article