PMID- 36820311 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230224 IS - 2694-2437 (Electronic) IS - 2694-2437 (Linking) VI - 3 IP - 1 DP - 2023 Feb 15 TI - Platelet Response to Allergens, CXCL10, and CXCL5 in the Context of Asthma. PG - 87-96 LID - 10.1021/acsbiomedchemau.2c00059 [doi] AB - 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 delta-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. CI - (c) 2022 The Authors. Published by American Chemical Society. FAU - Gruba, Sarah AU - Gruba S AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. FAU - Wu, Xiaojie AU - Wu X AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. FAU - Spanolios, Eleni AU - Spanolios E AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. FAU - He, Jiayi AU - He J AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. FAU - Xiong-Hang, Kang AU - Xiong-Hang K AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. FAU - Haynes, Christy L AU - Haynes CL AUID- ORCID: 0000-0002-5420-5867 AD - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. LA - eng PT - Journal Article DEP - 20221202 PL - United States TA - ACS Bio Med Chem Au JT - ACS bio & med chem Au JID - 9918232604406676 PMC - PMC9936497 COIS- The authors declare no competing financial interest. EDAT- 2023/02/24 06:00 MHDA- 2023/02/24 06:01 PMCR- 2022/12/02 CRDT- 2023/02/23 10:36 PHST- 2022/09/14 00:00 [received] PHST- 2022/11/15 00:00 [revised] PHST- 2022/11/16 00:00 [accepted] PHST- 2023/02/23 10:36 [entrez] PHST- 2023/02/24 06:00 [pubmed] PHST- 2023/02/24 06:01 [medline] PHST- 2022/12/02 00:00 [pmc-release] AID - 10.1021/acsbiomedchemau.2c00059 [doi] PST - epublish SO - ACS Bio Med Chem Au. 2022 Dec 2;3(1):87-96. doi: 10.1021/acsbiomedchemau.2c00059. eCollection 2023 Feb 15.