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Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3
Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Thoracic Society
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086046/ https://www.ncbi.nlm.nih.gov/pubmed/33556295 http://dx.doi.org/10.1165/rcmb.2020-0425OC |
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author | Shah, Sajeel A. Kanabar, Varsha Riffo-Vasquez, Yanira Mohamed, Zainab Cleary, Simon J. Corrigan, Christopher James, Alan L. Elliot, John G. Shute, Janis K. Page, Clive P. Pitchford, Simon C. |
author_facet | Shah, Sajeel A. Kanabar, Varsha Riffo-Vasquez, Yanira Mohamed, Zainab Cleary, Simon J. Corrigan, Christopher James, Alan L. Elliot, John G. Shute, Janis K. Page, Clive P. Pitchford, Simon C. |
author_sort | Shah, Sajeel A. |
collection | PubMed |
description | Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b(+) platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti–mouse CD49b-PE (phycoerythrin) antibody. Platelet–endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b(+) platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism. |
format | Online Article Text |
id | pubmed-8086046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Thoracic Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-80860462021-05-01 Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 Shah, Sajeel A. Kanabar, Varsha Riffo-Vasquez, Yanira Mohamed, Zainab Cleary, Simon J. Corrigan, Christopher James, Alan L. Elliot, John G. Shute, Janis K. Page, Clive P. Pitchford, Simon C. Am J Respir Cell Mol Biol Original Research Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b(+) platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti–mouse CD49b-PE (phycoerythrin) antibody. Platelet–endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b(+) platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism. American Thoracic Society 2021-05 /pmc/articles/PMC8086046/ /pubmed/33556295 http://dx.doi.org/10.1165/rcmb.2020-0425OC Text en Copyright © 2021 by the American Thoracic Society https://creativecommons.org/licenses/by/4.0/This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Shah, Sajeel A. Kanabar, Varsha Riffo-Vasquez, Yanira Mohamed, Zainab Cleary, Simon J. Corrigan, Christopher James, Alan L. Elliot, John G. Shute, Janis K. Page, Clive P. Pitchford, Simon C. Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title | Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title_full | Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title_fullStr | Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title_full_unstemmed | Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title_short | Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3 |
title_sort | platelets independently recruit into asthmatic lungs and models of allergic inflammation via ccr3 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086046/ https://www.ncbi.nlm.nih.gov/pubmed/33556295 http://dx.doi.org/10.1165/rcmb.2020-0425OC |
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