دورية أكاديمية

Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling.

التفاصيل البيبلوغرافية
العنوان: Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling.
المؤلفون: Esnault S; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Leet JP; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Johansson MW; Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Barretto KT; Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Fichtinger PS; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Fogerty FJ; Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Bernau K; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Mathur SK; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Mosher DF; Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.; Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Sandbo N; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA., Jarjour NN; Department of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
المصدر: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2020 Feb; Vol. 50 (2), pp. 198-212. Date of Electronic Publication: 2019 Dec 09.
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: Eosinophils/*immunology , Immunoglobulin G/*immunology , MAP Kinase Signaling System/*immunology , Microtubules/*immunology, Humans ; Interleukin-3/immunology ; Microtubule-Associated Proteins/immunology ; Reactive Oxygen Species/immunology ; Receptors, IgG/immunology ; rho-Associated Kinases
مستخلص: Background: The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell-free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that eosinophils have lysed and released cellular content, likely harming tissues.
Objective: The present study explores the mechanism of CD32- and αMß2 integrin-dependent eosinophil cytolysis of IL3-primed blood eosinophils seeded on heat-aggregated immunoglobulin G (HA-IgG).
Methods: Cytoskeletal events and signalling pathways potentially involved in cytolysis were assessed using inhibitors. The level of activation of the identified events and pathways involved in cytolysis was measured. In addition, the links between these identified pathways and changes in degranulation (exocytosis) and adhesion were analysed.
Results: Cytolysis of IL3-primed eosinophils was dependent on the production of reactive oxygen species (ROS) and downstream phosphorylation of p-38 MAPK. In addition, formation of microtubule (MT) arrays was necessary for cytolysis and was accompanied by changes in MT dynamics as measured by phosphorylation status of stathmin and microtubule-associated protein 4 (MAP4), the latter of which was regulated by ROS production. Reduced ROCK signalling preceded cytolysis, which was associated with eosinophil adhesion and reduced migration.
Conclusion and Clinical Relevance: In this CD32- and αMß2 integrin-dependent adhesion model, lysing eosinophils exhibit reduced migration and ROCK signalling, as well as both MT dynamic changes and p-38 phosphorylation downstream of ROS production. We propose that interfering with these pathways would modulate eosinophil cytolysis and subsequent eosinophil-driven tissue damage.
(© 2019 John Wiley & Sons Ltd.)
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معلومات مُعتمدة: UL1 RR025011 United States RR NCRR NIH HHS; UL1 TR002373 United States TR NCATS NIH HHS; P01 HL088594 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Eosinophil; IL3; adhesion; cytolysis; degranulation; immunoglobulin G; microtubule; priming
المشرفين على المادة: 0 (IL3 protein, human)
0 (Immunoglobulin G)
0 (Interleukin-3)
0 (MAP4 protein, human)
0 (Microtubule-Associated Proteins)
0 (Reactive Oxygen Species)
0 (Receptors, IgG)
EC 2.7.11.1 (rho-Associated Kinases)
تواريخ الأحداث: Date Created: 20191122 Date Completed: 20210609 Latest Revision: 20210609
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6994386
DOI: 10.1111/cea.13538
PMID: 31750580
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2222
DOI:10.1111/cea.13538