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
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