title: Sulfatides, L- and P-selectin ligands, exacerbate the intimal hyperplasia occurring after endothelial injury.
abstract: Leukocytes may be important in the development of intimal hyperplasia, but little is known about the participation of sulfatides (3-sulfated galactosyl ceramides) which are native ligands of L- and P-selectin. This study was designed to determine whether sulfatides affect the development of intimal hyperplasia. ICR mice were randomized to receive vehicle or sulfatides intravenously either at 1, 3, or 10 mg/kg/day for 7 days, or at 10 mg/kg/day for 1, 3, or 7 days. Endothelial damage was inflicted on the femoral artery via the photochemical reaction between rose bengal and green light. Scanning electron and light microscopic observations 3 days after the injury indicated that sulfatides-treated animals had more neutrophils adhering to the injury site than vehicle-treated controls. At 21 days, sulfatides-treated animals had a greater neointimal area than controls. In in vitro studies, sulfatides (i) increased cytosolic free calcium in mouse neutrophils, (ii) caused increases in expression of Mac-1 (CD 11 b/CD 18) on the neutrophil membrane surface in mouse whole blood. These findings suggest that neutrophil accumulation on the subendothelial matrix or adherence of platelets mediated by adhesive interactions between L- or P-selectin and sulfatides may contribute to the development of intimal hyperplasia. The neutrophil accumulation may be mediated by an increase in Mac-1 caused by the agonistic effects of sulfatides on the neutrophil membrane surface, or by an increase in L- and P-selectin ligands resulting from the binding of sulfatides onto the exposed subendothelial matrix.
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, 3600, Handa-cho, Hamamatsu 431-3124, Japan. shimazawa@gifu-pu.ac.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kondo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umemura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005263:Femoral Artery; D006965:Hyperplasia; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D010538:Peritonitis / Q000139:chemically induced / Q000517:prevention & control; D010973:Platelet Adhesiveness; D011897:Random Allocation; D013433:Sulfoglycosphingolipids / Q000008:administration & dosage / Q000494:pharmacology*; D013864:Thioglycolates; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D008024:Ligands; D019007:P-Selectin; D013433:Sulfoglycosphingolipids; D013864:Thioglycolates; D019041:L-Selectin; D002118:Calcium