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

Sarah Gruba, Xiaojie Wu, Eleni Spanolios, Jiayi He, Kang Xiong-Hang, Christy L. Haynes

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalACS Bio and Med Chem Au
Volume3
Issue number1
DOIs
StatePublished - Feb 15 2023

Bibliographical note

Funding Information:
The authors would like to acknowledge funding from the NIH Biotechnology Training grant (5T32GM008347-23) for S.M.G. and K.X., the UMN MRSEC (DMR-2011401) for J.H., the National Institutes of Health New Innovator Award (DP2 OD004258-01), and the Minnesota Nano Center for providing access to microfluidic fabrication equipment.

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

Keywords

  • allergen
  • chemokine
  • exocytosis
  • platelet
  • single cell

MRSEC Support

  • Partial

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma'. Together they form a unique fingerprint.

Cite this