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Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma

[Image: see text] Asthma is a chronic respiratory disease initiated by a variety of factors, including allergens. During an asthma attack, the secretion of C-X-C-motif chemokine 10 (CXCL10) and chemokine ligand 5 (CCL5) causes the migration of immune cells, including platelets, into the lungs and ai...

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Autores principales: Gruba, Sarah, Wu, Xiaojie, Spanolios, Eleni, He, Jiayi, Xiong-Hang, Kang, Haynes, Christy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936497/
https://www.ncbi.nlm.nih.gov/pubmed/36820311
http://dx.doi.org/10.1021/acsbiomedchemau.2c00059
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author Gruba, Sarah
Wu, Xiaojie
Spanolios, Eleni
He, Jiayi
Xiong-Hang, Kang
Haynes, Christy L.
author_facet Gruba, Sarah
Wu, Xiaojie
Spanolios, Eleni
He, Jiayi
Xiong-Hang, Kang
Haynes, Christy L.
author_sort Gruba, Sarah
collection PubMed
description [Image: see text] Asthma is a chronic respiratory disease initiated by a variety of factors, including allergens. During an asthma attack, the secretion of C-X-C-motif chemokine 10 (CXCL10) and chemokine ligand 5 (CCL5) causes the migration of immune cells, including platelets, into the lungs and airway. Platelets, which contain three classes of chemical messenger-filled granules, can secrete vasodilators (adenosine diphosphate and adenosine triphosphate), serotonin (a vasoconstrictor and a vasodilator, depending on the biological system), platelet-activating factor, N-formylmethionyl-leucyl-phenylalanine ((fMLP), a bacterial tripeptide that stimulates chemotaxis), and chemokines (CCL5, platelet factor 4 (PF4), and C-X-C-motif chemokine 12 (CXCL12)), amplifying the asthma response. The goal of this work was threefold: (1) to understand if and how the antibody immunoglobulin E (IgE), responsible for allergic reactions, affects platelet response to the common platelet activator thrombin; (2) to understand how allergen stimulation compares to thrombin stimulation; and (3) to monitor platelet response to fMLP and the chemokines CXCL10 and CCL5. Herein, high-pressure liquid chromatography with electrochemical detection and/or carbon-fiber microelectrode amperometry measured granular secretion events from platelets with and without IgE in the presence of the allergen 2,4,6-trinitrophenyl-conjugated ovalbumin (TNP-Ova), thrombin, CXCL10, or CCL5. Platelet adhesion and chemotaxis were measured using a microfluidic platform in the presence of CXCL10, CCL5, or TNP-OVA. Results indicate that IgE binding promotes δ-granule secretion in response to platelet stimulation by thrombin in bulk. Single-cell results on platelets with exogenous IgE exposure showed significant changes in the post-membrane–granule fusion behavior during chemical messenger delivery events after thrombin stimulation. In addition, TNP-Ova allergen stimulation of IgE-exposed platelets secreted serotonin to the same extent as thrombin platelet stimulation. Enhanced adhesion to endothelial cells was demonstrated by TNP-Ova stimulation. Finally, only after incubation with IgE did platelets secrete chemical messengers in response to stimulation with fMLP, CXCL10, and CCL5.
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spelling pubmed-99364972023-02-18 Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma Gruba, Sarah Wu, Xiaojie Spanolios, Eleni He, Jiayi Xiong-Hang, Kang Haynes, Christy L. ACS Bio Med Chem Au [Image: see text] Asthma is a chronic respiratory disease initiated by a variety of factors, including allergens. During an asthma attack, the secretion of C-X-C-motif chemokine 10 (CXCL10) and chemokine ligand 5 (CCL5) causes the migration of immune cells, including platelets, into the lungs and airway. Platelets, which contain three classes of chemical messenger-filled granules, can secrete vasodilators (adenosine diphosphate and adenosine triphosphate), serotonin (a vasoconstrictor and a vasodilator, depending on the biological system), platelet-activating factor, N-formylmethionyl-leucyl-phenylalanine ((fMLP), a bacterial tripeptide that stimulates chemotaxis), and chemokines (CCL5, platelet factor 4 (PF4), and C-X-C-motif chemokine 12 (CXCL12)), amplifying the asthma response. The goal of this work was threefold: (1) to understand if and how the antibody immunoglobulin E (IgE), responsible for allergic reactions, affects platelet response to the common platelet activator thrombin; (2) to understand how allergen stimulation compares to thrombin stimulation; and (3) to monitor platelet response to fMLP and the chemokines CXCL10 and CCL5. Herein, high-pressure liquid chromatography with electrochemical detection and/or carbon-fiber microelectrode amperometry measured granular secretion events from platelets with and without IgE in the presence of the allergen 2,4,6-trinitrophenyl-conjugated ovalbumin (TNP-Ova), thrombin, CXCL10, or CCL5. Platelet adhesion and chemotaxis were measured using a microfluidic platform in the presence of CXCL10, CCL5, or TNP-OVA. Results indicate that IgE binding promotes δ-granule secretion in response to platelet stimulation by thrombin in bulk. Single-cell results on platelets with exogenous IgE exposure showed significant changes in the post-membrane–granule fusion behavior during chemical messenger delivery events after thrombin stimulation. In addition, TNP-Ova allergen stimulation of IgE-exposed platelets secreted serotonin to the same extent as thrombin platelet stimulation. Enhanced adhesion to endothelial cells was demonstrated by TNP-Ova stimulation. Finally, only after incubation with IgE did platelets secrete chemical messengers in response to stimulation with fMLP, CXCL10, and CCL5. American Chemical Society 2022-12-02 /pmc/articles/PMC9936497/ /pubmed/36820311 http://dx.doi.org/10.1021/acsbiomedchemau.2c00059 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Gruba, Sarah
Wu, Xiaojie
Spanolios, Eleni
He, Jiayi
Xiong-Hang, Kang
Haynes, Christy L.
Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title_full Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title_fullStr Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title_full_unstemmed Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title_short Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma
title_sort platelet response to allergens, cxcl10, and cxcl5 in the context of asthma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936497/
https://www.ncbi.nlm.nih.gov/pubmed/36820311
http://dx.doi.org/10.1021/acsbiomedchemau.2c00059
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