SEARCH:   Advanced

Blood, 1 June 2008, Vol. 111, No. 11, pp. 5264-5265. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Voorberg, J. Search for Related Content PubMed PubMed Citation Articles by Voorberg, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS Comment on Babich et al, page 5282 Slipping out the Weibel-Palade body Jan Voorberg SANQUIN-AMC LANDSTEINER LABORATORY In this issue of Blood, Babich and colleagues disclose an elegant mechanism that serves to selectively release cargo from WPBs. Weibel-Palade bodies (WPBs) are versatile storage organelles within endothelial cells that release their inflammatory and prothrombotic content into the circulation in response to a large number of agonists.1 Using real-time analysis of fluorescently tagged von Willebrand factor (VWF) and VWF propolypeptide, Babich et al nicely show that a proportion of WPBs transiently fuse with the plasma membrane during a "lingering kiss." Fusion pores of approximately 12 nm in diameter are generated that facilitate the selective release of low-molecular-weight components like IL-8 from these organelles. An important physiological implication of these findings is that endothelial cells can selectively release proinflammatory cytokines like IL-8 and eotaxin-3 while retaining prothrombotic VWF. The selective release of small-core and membrane proteins comes at a cost, though; the elegantly shaped, cigarlike WPBs collapse into ordinary, circular vesicles. In the original study by Weibel and Palade, the presence of tubular structures was noted.2 It has recently been shown that the tubules present within these organelles are hollow cylinders that are created by propolypeptide-guided condensation of VWF.3,4 The integrity of VWF-containing tubules that maintain the elongated form of WPBs is critically dependent on a low pH. The pH within WPBs during a lingering kiss increases considerably, and this most likely results in the so-called unfurling of tubules into long VWF filaments.3 Although this has not been addressed, it is likely that the increase in intracellular pH results in the rapid disappearance of VWF tubules (see figure). The morphological characteristics of these collapsed WPBs have not been determined. Therefore, it is presently unknown whether this class of WPBs can reassemble into rod-shaped structures, fuse with newly formed organelles, or exocytose following application of a more rigorous stimulus. View larger version (77K): [in this window] [in a new window]   Selective release of small molecules (indicated in orange and red) during transient fusion of WPBs with the plasma membrane. During fusion elongated WPBs collapse into circular structures, designated collapsed WPBs. This most likely is due to the conversion of highly organized VWF tubules (thick black lines in left panel) into randomly organized VWF polymers (black curved lines in middle and right panels).   In their visually appealing article, Babich and coworkers show that lingering kisses account for 10% to 25% of all fusion events following stimulation with histamine. A large number of agonists can provoke release of WPBs. Clinically, this is exploited by the administration of desmopressin (DDAVP) to patients with von Willebrand disease or mild hemophilia A. Under these conditions, the release of WPBs is induced by cAMP-dependent signaling pathways that result in only modest activation of signaling molecules involved in regulation of WPB exocytosis.1 It will be interesting to determine whether, under these conditions, transient fusion of WPBs with the plasma membrane will occur at a higher frequency than observed following stimulation with histamine. Overall, the findings of Babich et al highlight yet another fascinating aspect of the biology of the uniquely shaped WPB. Their study provides an excellent starting point to further explore the regulation and physiological significance of release of WPBs with different proinflammatory and vasoregulatory cargo. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Rondaij MG, Bierings R, Kragt A, van Mourik JA, Voorberg J. Dynamics and plasticity of Weibel-Palade bodies in endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26:1002–1007.[Abstract/Free Full Text] Weibel ER, Palade GE. New cytoplasmic components in arterial endothelia. J Cell Biol. 1964;23:101–112.[Abstract/Free Full Text] Michaux G, Abbitt KB, Collinson LM, Haberichter SL, Norman KE, Cutler DF. The physiological function of von Willebrand's factor depends on ist tubular storage in endothelial Weibel-Palade bodies. Dev Cell. 2006;10:223–232.[CrossRef][Medline] [Order article via Infotrieve] Huang RH, Wang Y, Roth R, et al. Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor. Proc Natl Acad Sci U S A. 2008;105:482–487.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Selective release of molecules from Weibel-Palade bodies during a lingering kiss Victor Babich, Athinoula Meli, Laura Knipe, John E. Dempster, Paul Skehel, Matthew J. Hannah, and Tom Carter Blood 2008 111: 5282-5290. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Voorberg, J. Search for Related Content PubMed PubMed Citation Articles by Voorberg, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020