title: Interleukin-1 inhibits the synthesis of von Willebrand factor in endothelial cells, which results in a decreased reactivity of their matrix toward platelets.
abstract: We have studied the influence of recombinant human and murine interleukin-1 (IL-1) on the synthesis and secretion of von Willebrand factor by human endothelial cells. Treatment of endothelial cells with IL-1 caused a decline in the steady-state level of von Willebrand factor mRNA in endothelial cells. This decline resulted in a decreased secretion to the culture medium, a decreased storage of von Willebrand factor in the Weibel-Palade bodies, and a decreased incorporation into the extracellular matrix. As a consequence of the decreased amount of von Willebrand factor in the extracellular matrix we have found a strongly impaired platelet adhesion to these matrices. When the matrices of IL-1-treated cells were incubated with purified von Willebrand factor, their ability to support platelet adhesion was restored. These results suggest that perturbation of endothelial cells by inflammatory mediators like IL-1 results in a decreased adhesion of platelets to the subendothelium owing to a diminished synthesis of von Willebrand factor.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
authors.forename: P P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: H C
authors.initials: HC
authors.lastname: de Boer
authors.forename: D M
authors.initials: DM
authors.lastname: Stern
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D014841:von Willebrand Factor; D011464:Epoprostenol