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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2223. 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 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 Lowenstein, C. J. Search for Related Content PubMed Articles by Lowenstein, C. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Next Article  HEMOSTASIS Comment on Dole et al, page 2334 Platelets trigger endothelial exocytosis Charles J. Lowenstein THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE Dole and colleagues report that activated platelets stimulate endothelial secretion of Weibel-Palade bodies, causing leukocyte rolling in vivo. This discovery strengthens the connection between thrombosis and vascular inflammation. Do platelets play a critical role in vascular inflammation? Activated platelets circulate in the blood of patients with a variety of inflammatory diseases, including sepsis, diabetes, and atherosclerosis. Inflammatory stimuli can activate platelets, promoting a prothrombotic state, but studies also suggest that activated platelets can modulate vascular inflammation. Activated platelets release proinflammatory cytokines and chemokines such as interleukin-1, CD40 ligand (CD40L), and CC chemokine ligand 5 (CCL5).1-3 However, the precise cellular mechanisms by which platelets trigger vascular inflammation are not fully understood. In this issue of Blood, Dole and colleagues report that activated platelets stimulate endothelial exocytosis. Activated platelets infused into mice triggered endothelial secretion of Weibel-Palade bodies, externalizing P-selectin and releasing von Willebrand factor (VWF) in mouse venules. Endothelial exocytosis in turn caused leukocyte rolling along venules (see figure). This study extends prior work showing that activated platelets increased monocyte adhesion to endothelial cells in vitro,4 and it also fits nicely with a previous study which demonstrated that platelets triggered leukocyte adherence to endothelium overlying atherosclerotic plaques.5 View larger version (77K): [in this window] [in a new window]   Activated platelets trigger endothelial exocytosis, externalizing P-selectin, which mediates leukocyte rolling. Illustration by A. Y. Chen.   Platelets thus activate endothelial exocytosis. How? Do platelets directly contact endothelial cells, triggering exocytosis? Do platelets release soluble mediators that stimulate endothelial-cell secretion? Or perhaps platelets indirectly trigger endothelial release of Weibel-Palade bodies by activating leukocytes, which in turn stimulate the endothelium. Dole and colleagues' current study supports this last concept: platelet P-selectin was necessary for endothelial activation, suggesting that platelet interaction with leukocytes through leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) might be important in prompting endothelial secretion. The current study strengthens the connection between thrombosis and vascular inflammation. Activated platelets not only release cytokines that modulate delayed endothelial expression of proinflammatory genes, but also initiate immediate vascular responses such as endothelial granule exocytosis. Further exploration of the mechanisms by which activated platelets trigger endothelial exocytosis will lead to novel therapies for inflammatory diseases such as sepsis and atherosclerosis. References Hawrylowicz CM, Howells GL, Feldmann M. Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production. J Exp Med. 1991;174: 785-790.[Abstract/Free Full Text] Henn V, Slupsky JR, Grafe M, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998;391: 591-594.[CrossRef][Medline] [Order article via Infotrieve] Ramos CL, Huo Y, Jung U, et al. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice. Circ Res. 1999;84: 1237-1244.[Abstract/Free Full Text] Theilmeier G, Lenaerts T, Remacle C, Collen D, Vermylen J, Hoylaerts MF. Circulating activated platelets assist THP-1 monocytoid/endothelial cell interaction under shear stress. Blood. 1999;94: 2725-2734.[Abstract/Free Full Text] Huo Y, Schober A, Forlow SB, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med. 2003;9: 61-67.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Activated platelets induce Weibel-Palade–body secretion and leukocyte rolling in vivo: role of P-selectin Vandana S. Dole, Wolfgang Bergmeier, Heather A. Mitchell, Sarah C. Eichenberger, and Denisa D. Wagner Blood 2005 106: 2334-2339. [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 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 Lowenstein, C. J. Search for Related Content PubMed Articles by Lowenstein, C. J. 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