Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important role in recurrent coronary arterial thrombosis in dogs
| Autor: | Hideo Yasukawa, Shinichiro J. Tojo, Takahisa Ueyama, Nobuya Haramaki, Takafumi Ueno, Tsutomu Imaizumi, Atsushi Katoh, Hisao Ikeda, Ichiro Onitsuka, Toyoaki Murohara, Yoshinori Takajo, Hiroyuki Eguchi |
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| Rok vydání: | 1999 |
| Předmět: |
Blood Platelets
Microscopy Electron Scanning Transmission Pathology medicine.medical_specialty Time Factors Endothelium P-selectin Oligosaccharides Pharmacology chemistry.chemical_compound Dogs Recurrence medicine Cell Adhesion Animals Platelet Thrombus Sialyl Lewis X Antigen business.industry Cell adhesion molecule Coronary Thrombosis medicine.disease Thrombosis Coronary Vessels P-Selectin medicine.anatomical_structure Sialyl-Lewis X chemistry Cardiology and Cardiovascular Medicine business Selectin |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 19(4) |
| ISSN: | 1079-5642 |
| Popis: | Abstract —Cell adhesion molecules may play an important role in the disease process of acute coronary syndromes. We have shown a neutralizing anti-P-selectin monoclonal antibody and a sialyl Lewis x -containing oligosaccharide (SLe x -OS), an analogue of selectin ligand on leukocytes, reduce cyclic flow variations (CFVs) in a canine model of recurrent coronary arterial thrombosis, suggesting the important interaction between P-selectin and SLe x for the pathophysiology of these syndromes. However, the functional role of these adhesion molecules in the thrombotic process remains unclear. Therefore, we investigated effects of SLe x -OS on CFVs, platelet P-selectin expression, and morphology of the stenotic site in the same model. Anesthetized open-chest dogs (n=34) were randomly divided into 4 groups after developing CFVs. Dogs intravenously received saline or graded doses of SLe x -OS (5, 20, or 40 mg/kg bolus) infusion followed by a continuous infusion (5 mg · kg −1 · h −1 ) for 60 minutes. By flow cytometric analysis, P-selectin expression on platelets after CFVs was significantly upregulated during CFVs. Immunohistochemical analysis revealed the incorporation of platelets with upregulated P-selectin within thrombi at the stenotic site. Microscopic observations revealed the presence of numerous platelets adhered to leukocytes at the stenotic site on the damaged endothelium. SLe x -OS significantly reduced CFVs, inhibited the P-selectin expression on platelets, and prevented the adherence of platelets and leukocytes. These findings further support the notion that the adhesive interaction between P-selectin on platelets and SLe x on leukocytes plays an important role in platelet-mediated thrombus formation in this model. |
| Databáze: | OpenAIRE |
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