دورية أكاديمية
أعرض في EDS

An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells.

التفاصيل البيبلوغرافية
العنوان: An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells.
المؤلفون: Kerr SC; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA., Gonzalez JR; Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA., Schanin J; Allakos. Inc, Redwood City, CA, USA., Peters MC; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA., Lambrecht BN; VIB Center for Inflammation Research, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Brock EC; Allakos. Inc, Redwood City, CA, USA., Charbit A; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA., Ansel KM; Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA., Youngblood BA; Allakos. Inc, Redwood City, CA, USA., Fahy JV; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA.
المصدر: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2020 Aug; Vol. 50 (8), pp. 904-914. Date of Electronic Publication: 2020 Jul 08.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8906443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2222 (Electronic) Linking ISSN: 09547894 NLM ISO Abbreviation: Clin Exp Allergy Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Blackwell Scientific Publications, c1989-
مواضيع طبية MeSH: Anti-Asthmatic Agents/*pharmacology , Antibodies, Monoclonal, Humanized/*pharmacology , Asthma/*drug therapy , Eosinophils/*drug effects , Lectins/*antagonists & inhibitors , Lung/*drug effects , Mast Cells/*drug effects, Adult ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Antigens, CD/genetics ; Antigens, CD/immunology ; Antigens, CD/metabolism ; Antigens, Differentiation, B-Lymphocyte/genetics ; Antigens, Differentiation, B-Lymphocyte/immunology ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Apoptosis/drug effects ; Asthma/immunology ; Asthma/metabolism ; Case-Control Studies ; Cells, Cultured ; Eosinophils/immunology ; Eosinophils/metabolism ; Female ; Humans ; Lectins/genetics ; Lectins/immunology ; Lectins/metabolism ; Lung/immunology ; Lung/metabolism ; Male ; Mast Cells/immunology ; Mast Cells/metabolism ; Middle Aged ; Receptors, IgE/genetics ; Receptors, IgE/metabolism ; Sputum/cytology ; Young Adult
مستخلص: Background: Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is expressed on mast cells and eosinophils, but information about Siglec-8 expression and function in the lung is limited. A humanized antibody, AK002, targeting Siglec-8 is undergoing development for treatment of diseases associated with mast cell and eosinophil-driven inflammation.
Objective: To characterize Siglec-8 expression in the airway in asthma and determine whether antibodies that target Siglec-8 (S8mAbs) can decrease airway eosinophils in asthma or inhibit lung mast cell activation.
Methods: Gene expression profiling and flow cytometry were used to characterize Siglec-8 expression in sputum cells from stable asthma. An antibody-dependent cellular cytotoxicity (ADCC) assay was used to determine whether an S8mAb can decrease eosinophils in sputum from asthma patients ex vivo. A mast cell activation assay was used to determine whether an S8mAb can inhibit mast cell activation in human lung tissue ex vivo.
Results: Gene expression for Siglec-8 is increased in sputum cells in asthma and correlates with gene expression for eosinophils and mast cells. Gene expression for Siglec-8 is inversely and significantly correlated with measures of airflow obstruction in asthma patients. Siglec-8 is prominently expressed on the surface of eosinophils and mast cells in sputum. S8mAbs decrease eosinophils in sputum from patients with asthma and inhibit FcεR1-activated mast cells in lung tissues.
Conclusions and Clinical Relevance: Siglec-8 is highly expressed on eosinophils and mast cells in asthmatic sputum and targeting Siglec-8 with an antibody is a plausible strategy to decrease sputum eosinophils and inhibit lung mast cells in asthma.
(© 2020 John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 789384 International ERC_ European Research Council; K23 HL138303 United States HL NHLBI NIH HHS; P01 HL107202 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: asthma; basic immunology; basophil; eosinophils; mast cells
المشرفين على المادة: 0 (AK002)
0 (Anti-Asthmatic Agents)
0 (Antibodies, Monoclonal, Humanized)
0 (Antigens, CD)
0 (Antigens, Differentiation, B-Lymphocyte)
0 (Lectins)
0 (Receptors, IgE)
0 (SIGLEC8 protein, human)
تواريخ الأحداث: Date Created: 20200617 Date Completed: 20211101 Latest Revision: 20211101
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7610812
DOI: 10.1111/cea.13681
PMID: 32542913
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2222
DOI:10.1111/cea.13681