title: Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important role in recurrent coronary arterial thrombosis in dogs.
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 SLex 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.
authors: Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. ikeikeda@med.kurume-u.ac.jp
authors: H
authors: H
authors: Ikeda
authors: T
authors: T
authors: Ueyama
authors: T
authors: T
authors: Murohara
authors: H
authors: H
authors: Yasukawa
authors: N
authors: N
authors: Haramaki
authors: H
authors: H
authors: Eguchi
authors: A
authors: A
authors: Katoh
authors: Y
authors: Y
authors: Takajo
authors: I
authors: I
authors: Onitsuka
authors: T
authors: T
authors: Ueno
authors: S J
authors: SJ
authors: Tojo
authors: T
authors: T
authors: Imaizumi
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion; D003328:Coronary Thrombosis / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000648:ultrastructure; D004285:Dogs; D017348:Microscopy, Electron, Scanning Transmission; D009844:Oligosaccharides / Q000097:blood*; D019007:P-Selectin / Q000096:biosynthesis / Q000097:blood*; D012008:Recurrence; D000080506:Sialyl Lewis X Antigen; D013997:Time Factors
chemical_list: D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen