title: Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.
abstract: It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF) in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP), would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.
authors: Department of Bioengineering, Rice University, Houston, Texas, United States of America.
authors: Nancy A
authors: NA
authors: Turner
authors: Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer and Hematology Centers, Houston, Texas, United States of America; Baylor College of Medicine, Houston, Texas, United States of America.
authors: Sarah E
authors: SE
authors: Sartain
authors: Baylor College of Medicine, Houston, Texas, United States of America; Division of Transfusion Medicine and Coagulation, Texas Children's Hospital, Houston, Texas, United States of America.
authors: Shiu-Ki
authors: SK
authors: Hui
authors: Department of Bioengineering, Rice University, Houston, Texas, United States of America; Baylor College of Medicine, Houston, Texas, United States of America.
authors: Joel L
authors: JL
authors: Moake
mesh_terms: D017242:Complement Factor H / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D003593:Cytoplasm / Q000378:metabolism*; D042783:Endothelial Cells / Q000276:immunology*; D005340:Fibrinogen / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007118:Immunoassay; D008856:Microscopy, Fluorescence; D020302:Weibel-Palade Bodies / Q000378:metabolism
chemical_list: D017242:Complement Factor H; D005340:Fibrinogen