Information de reference pour ce titreAccession Number: | 00043605-199907000-00028.
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Author: | Rosnoblet, Corinne; Vischer, Ulrich M.; Gerard, Robert D.; Irminger, Jean-Claude; Halban, Philippe A.; Kruithof, Egbert K.O.
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Institution: | From the Division of Angiology and Hemostasis (C.R., E.K.O.K.), Division of Clinical Biochemistry (U.M.V.) and Louis Jeantet Research Laboratories (J.-C.I., P.A.H.), University Hospital Geneva, Switzerland, and the Center for Transgene Technology and Gene Therapy, Leuven, Belgium (R.D.G.).
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Title: | Storage of Tissue-Type Plasminogen Activator in Weibel-Palade Bodies of Human Endothelial Cells.[Miscellaneous Article]
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Source: | Arteriosclerosis, Thrombosis & Vascular Biology. 19(7):1796-1803, July 1999.
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Abstract: | Tissue-type plasminogen activator (t-PA) is acutely released by endothelial cells. Although its endothelial storage compartment is still not well defined, t-PA release is often accompanied by release of von Willebrand factor (vWf), a protein stored in Weibel-Palade bodies. We investigated, therefore, whether t-PA is stored in these secretory organelles. Under basal culture conditions, a minority of human umbilical vein endothelial cells (HUVEC) exhibited immunofluorescent staining for t-PA, which was observed only in Weibel-Palade bodies. To increase t-PA expression, HUVEC were infected with a t-PA recombinant adenovirus (AdCMVt-PA). Overexpressed t-PA was detected in Weibel-Palade bodies and acutely released together with endogenous vWf by thrombin or calcium ionophore stimulation. In contrast, plasminogen activator inhibitor type 1 and urokinase were not detected in Weibel-Palade bodies after adenovirus-mediated overexpression. Infection of HUVEC with proinsulin recombinant adenovirus resulted in the storage of insulin in Weibel-Palade bodies, indicating that these organelles can also store nonendothelial proteins that show regulated secretion. Infection of AtT-20 pituitary cells, a cell type with regulated secretion, with AdCMVt-PA resulted in the localization of t-PA in adrenocorticotropic hormone-containing granules, indicating that t-PA can be diverted to secretory granules independently of vWf. Coinfection of AtT-20 cells with AdCMVt-PA and proinsulin recombinant adenovirus resulted in the colocalization of t-PA and insulin in the same granules. Taken together, these results suggest that HUVEC have protein sorting mechanisms similar to those of other regulated secretory cells. Although the results did not exclude an alternative storage site for t-PA in HUVEC, they established that t-PA can be stored in Weibel-Palade bodies. This finding may explain the acute coordinate secretion of t-PA and vWf.
(C) 1999 American Heart Association, Inc.
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Author Keywords: | tissue-type plasminogen activator; von Willebrand factor; Weibel-Palade bodies; endothelial cells; immunofluorescence.
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Language: | English.
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Document Type: | Thrombosis.
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Journal Subset: | Clinical Medicine.
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ISSN: | 1079-5642
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NLM Journal Code: | 9505803, B89
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