title: Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells.
abstract: Microvascular complications in sickle cell disease occur as a result of obstruction of small vessels by deoxygenated sickle cells. Cerebrovascular complications are also common and result from obstruction of large blood vessels by thrombosis with changes in vessels that have some similarity to those found in arteriosclerotic vascular disease. Endothelial damage and activation from sickle cell-endothelial interactions may contribute to both. We find that endothelial cells have increased expression of VCAM-1, E-selectin, and ICAM-1 when exposed to sickle blood cells. The concentration-dependent, sickle-induced, adhesion molecule expression is significantly greater than that promoted by normal cells. The time course of Cell Adhesion Molecule (CAM) expression is similar to that induced by TNF-alpha and IL1. Studies after white cell enrichment and reduction suggest leukocytes are the primary mediators. CAM expression by endothelial cells appears stimulated by soluble factors. Antibody inhibition studies support TNF-alpha and IL-1, produced by sickle leukocytes, as the primary soluble factors responsible for the observed CAM expression. Both the induction of endothelial CAM expression and subsequent endothelial adherence of sickle erythrocytes may play significant roles in the pathophysiology of sickle-related complications, and reduction in CAM expression may provide a new approach to treatment.
authors.affiliation: School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Brown
authors.forename: T M
authors.initials: TM
authors.lastname: Wick
authors.forename: J R
authors.initials: JR
authors.lastname: Eckman
mesh_terms: D000755:Anemia, Sickle Cell / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D012156:Reticulocytes / Q000378:metabolism / Q000473:pathology; D013010:Sonication; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D019040:E-Selectin; D039041:Integrin alpha4beta1; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011112:Polymyxin B