Necessity of Thromboxane A2 for Initiation of Platelet-Mediated Contact Sensitivity: Dual Activation of Platelets and Vascular Endothelial Cells
Autor: | Motoki Mitsuhashi, Shuzo Sawada, Mikio Takaku, Takasi Hironaka, Hiroshi Matsuda, Keiko Kawamoto, Atsuko Itakura, Chie Fujisawa, Akane Tanaka |
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Rok vydání: | 2001 |
Předmět: |
Blood Platelets
Male Agonist Serotonin medicine.medical_specialty Injections Intradermal medicine.drug_class Thromboxane Receptors Thromboxane Immunology Carbazoles Vascular Cell Adhesion Molecule-1 Aorta Thoracic Biology Dermatitis Contact Mice Thromboxane A2 chemistry.chemical_compound Adenosine Triphosphate In vivo Internal medicine medicine Animals Humans Vasoconstrictor Agents Immunology and Allergy Platelet Aorta Abdominal Intradermal injection Cells Cultured Sulfonamides Immune Sera Ear Intercellular Adhesion Molecule-1 Platelet Activation Receptor antagonist Mice Mutant Strains In vitro Mice Inbred C57BL Endocrinology chemistry 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Injections Intravenous Endothelium Vascular Injections Intraperitoneal Platelet Aggregation Inhibitors |
Zdroj: | The Journal of Immunology. 166:617-623 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.166.1.617 |
Popis: | To investigate the crucial role of platelet-derived thromboxane A2 (TXA2) in initiating Ag-specific contact sensitivity (CS), a platelet-dependent CS model using genetically mast cell-deficient W/Wv mice, was provided. In vivo treatment with BAYu3405, a TXA2 receptor antagonist, markedly suppressed CS responses in a dose-dependent manner. This inhibitory effect occurred when BAYu3405 was administered before an early initiating phase, suggesting that TXA2 may be a potent initiator of platelet-mediated CS responses. When platelets were pretreated with BAYu3405 in vitro, platelet aggregation as well as serotonin release, which is able to induce the early phase response allowing local recruitment of CS effector T cells due to direct activation of vascular endothelial cells, was inhibited. The addition of U46619, a TXA2 agonist, or a mixture of platelets and thrombin-enhanced expression of both ICAM-1 and VCAM-1 on isolated mouse aortic endothelial cells, which was completely abolished by pretreatment with BAYu3405. Furthermore, intradermal injection of U46619 into the ear of platelet-depleted mice led to CS responses with marked expression of ICAM-1 and VCAM-1 on the vascular endothelium. These findings suggest that TXA2 generated from platelets activated with Ag may mediate initiation of CS responses through inducing serotonin release from platelets and the subsequent aggregation and up-regulated expression of ICAM-1 and VCAM-1 on vascular endothelial cells. |
Databáze: | OpenAIRE |
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