(Circulation. 1995;92:3304-3311.)
© 1995 American Heart Association, Inc.
Articles |
Peptido-Leukotrienes Are Potent Agonists of von Willebrand Factor Secretion and P-Selectin Surface Expression in Human Umbilical Vein Endothelial Cells
From the Hematology-Oncology Division, Brigham and Women's Hospital, and Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Mass.
Correspondence to Bruce M. Ewenstein, MD, PhD, Hematology-Oncology Division, or Charles N. Serhan, PhD; new address: Center for Experimental Therapeutics and Reperfusion Injury, 75 Francis St, Boston, MA 02115.
Background The peptido-leukotrienes (LTs) and lipoxins (LX) are produced by platelets through the transcellular conversion of leukocyte-derived LTA4 at sites of vascular inflammation and injury, such as during coronary artery balloon angioplasty. We studied the actions of these eicosanoids on vascular endothelium.
Methods and Results We found that stimulation of cultured human umbilical vein endothelial cells (EC) with LTC4 and LTD4 resulted in the release of high-molecular-weight multimers of von Willebrand factor (vWF) in a concentration- and time-dependent fashion, as measured by ELISA. Neither LXA4 nor LXB4 stimulated vWF release. LTC4 and LTD4 also stimulated a rapid increase in the surface expression of P-selectin indicated by increased binding of anti–P-selectin monoclonal antibody–coated beads. Fluorescence cytometry detected prolonged peaks of [Ca2+]i in EC in response to concentrations of thrombin and LTD4 that induce near-maximal vWF secretion. In contrast, concentrations of LTC4 that induce similar levels of vWF secretion produced only asynchronous oscillations of [Ca2+]i in most EC and rarely induced prolonged peaks of [Ca2+]i. Depletion of external Ca2+ had no apparent impact on LT-stimulated [Ca2+]i transients and vWF secretion, implicating an intracellular pool as the source of this response. Staurosporine, sphingosine, and H-7 each had only modest effects on peptido-LT–induced vWF secretion, suggesting that protein kinase C is not a primary mediator of peptido-LT–induced exocytosis. Inhibitors of cyclooxygenase and platelet-activating factor had no effect on peptido-LT–mediated vWF secretion.
Conclusions Through the induction of vWF secretion and P-selectin surface expression, peptido-LTs are likely to play an important role in the interrelated processes of hemostasis and inflammation.
Key Words: von Willebrand factor • secretion • leukotriene • eicosanoid • transcellular metabolism
This article has been cited by other articles:
 |
|
 |
|
  N. Patel, C. S. Gonsalves, M. Yang, P. Malik, and V. K. Kalra Placenta growth factor induces 5-lipoxygenase-activating protein to increase leukotriene formation in sickle cell disease Blood, January 29, 2009; 113(5): 1129 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Santilli, M. Romano, A. Recchiuti, A. Dragani, A. Falco, G. Lessiani, F. Fioritoni, S. Lattanzio, D. Mattoscio, R. De Cristofaro, et al. Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients Blood, August 15, 2008; 112(4): 1085 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Woszczek, L.-Y. Chen, S. Nagineni, S. Alsaaty, A. Harry, C. Logun, R. Pawliczak, and J. H. Shelhamer IFN-{gamma} Induces Cysteinyl Leukotriene Receptor 2 Expression and Enhances the Responsiveness of Human Endothelial Cells to Cysteinyl Leukotrienes J. Immunol., April 15, 2007; 178(8): 5262 - 5270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Rondaij, R. Bierings, A. Kragt, J. A. van Mourik, and J. Voorberg Dynamics and Plasticity of Weibel-Palade Bodies in Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1002 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Yiming, K. Parthasarathi, A. C. Issekutz, and S. Bhattacharya Sequence of Endothelial Signaling during Lung Expansion Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 549 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Dole, W. Bergmeier, H. A. Mitchell, S. C. Eichenberger, and D. D. Wagner Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin Blood, October 1, 2005; 106(7): 2334 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsushita, C. N. Morrell, and C. J. Lowenstein A Novel Class of Fusion Polypeptides Inhibits Exocytosis Mol. Pharmacol., April 1, 2005; 67(4): 1137 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hui, Y. Cheng, I. Smalera, W. Jian, L. Goldhahn, G. A. FitzGerald, and C. D. Funk Directed Vascular Expression of Human Cysteinyl Leukotriene 2 Receptor Modulates Endothelial Permeability and Systemic Blood Pressure Circulation, November 23, 2004; 110(21): 3360 - 3366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bhatia, K. Matsushita, M. Yamakuchi, C. N. Morrell, W. Cao, and C. J. Lowenstein Ceramide Triggers Weibel-Palade Body Exocytosis Circ. Res., August 6, 2004; 95(3): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Rondaij, E. Sellink, K. A. Gijzen, J. P. ten Klooster, P. L. Hordijk, J. A. van Mourik, and J. Voorberg Small GTP-Binding Protein Ral Is Involved in cAMP-Mediated Release of von Willebrand Factor From Endothelial Cells Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1315 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sjostrom, A.-S. Johansson, O. Schroder, H. Qiu, J. Palmblad, and J. Z. Haeggstrom Dominant Expression of the CysLT2 Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): e37 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lotzer, R. Spanbroek, M. Hildner, A. Urbach, R. Heller, E. Bretschneider, H. Galczenski, J. F. Evans, and A. J.R. Habenicht Differential Leukotriene Receptor Expression and Calcium Responses in Endothelial Cells and Macrophages Indicate 5-Lipoxygenase-Dependent Circuits of Inflammation and Atherogenesis Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): e32 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Radmark 5-Lipoxygenase-Derived Leukotrienes: Mediators Also of Atherosclerotic Inflammation Arterioscler Thromb Vasc Biol, June 1, 2003; 23(7): 1140 - 1142. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Brink, S.-E. Dahlen, J. Drazen, J. F. Evans, D. W. P. Hay, S. Nicosia, C. N. Serhan, T. Shimizu, and T. Yokomizo International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors Pharmacol. Rev., March 1, 2003; 55(1): 195 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Spanbroek, R. Grabner, K. Lotzer, M. Hildner, A. Urbach, K. Ruhling, M. P. W. Moos, B. Kaiser, T. U. Cohnert, T. Wahlers, et al. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis PNAS, February 4, 2003; 100(3): 1238 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhattacharya, N. Sen, M. T. Yiming, R. Patel, K. Parthasarathi, S. Quadri, A. C. Issekutz, and J. Bhattacharya High Tidal Volume Ventilation Induces Proinflammatory Signaling in Rat Lung Endothelium Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 218 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P Vallely, P. G Bannon, C. F Hughes, and L. Kritharides Endothelial Cell Adhesion Molecules and Cardiopulmonary Bypass Asian Cardiovasc Thorac Ann, December 1, 2001; 9(4): 349 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Rosenberg, J. S. Greengard, and R. R. Montgomery Genetic Induction of a Releasable Pool of Factor VIII in Human Endothelial Cells Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2689 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Newsholme, D. T. Thudium, K. A. Gossett, E. S. Watson, and L. W. Schwartz Evaluation of Plasma von Willebrand Factor as a Biomarker for Acute Arterial Damage in Rats Toxicol Pathol, September 1, 2000; 28(5): 688 - 693. [Abstract] [PDF]
|
|
|
|
|
|
S. Schnyder-Candrian, L. Borsig, R. Moser, and E. G. Berger Localization of alpha 1,3-fucosyltransferase VI in Weibel-Palade bodies of human endothelial cells PNAS, July 18, 2000; 97(15): 8369 - 8374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]
|
|
|
|
|
|
A. D. Blann, F. Li-Saw-Hee, G. Y.H. Lip, T. Minamino, M. Kitakaze, S. Sanada, H. Asanuma, T. Kurotobi, Y. Koretsune, M. Fukunami, et al. Increased Membrane and Soluble P-Selectin in Atrial Fibrillation • Response Circulation, October 26, 1999; 100 (17): e86 - e87. [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Datta, H. Youssoufian, P. W. Marks, and B. M. Ewenstein Targeting of a Heterologous Protein to a Regulated Secretion Pathway in Cultured Endothelial Cells Blood, October 15, 1999; 94(8): 2696 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Marleau, B. Fruteau de Laclos, A. B. Sanchez, P. E. Poubelle, and P. Borgeat Role of 5-Lipoxygenase Products in the Local Accumulation of Neutrophils in Dermal Inflammation in the Rabbit J. Immunol., September 15, 1999; 163(6): 3449 - 3458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Davi, M. Romano, A. Mezzetti, A. Procopio, S. Iacobelli, T. Antidormi, T. Bucciarelli, P. Alessandrini, F. Cuccurullo, and G. B. Bon Increased Levels of Soluble P-Selectin in Hypercholesterolemic Patients Circulation, March 17, 1998; 97(10): 953 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Vischer and C. B. Wollheim Purine Nucleotides Induce Regulated Secretion of von Willebrand Factor: Involvement of Cytosolic Ca2+ and Cyclic Adenosine Monophosphate-Dependent Signaling in Endothelial Exocytosis Blood, January 1, 1998; 91(1): 118 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Eppihimer, J. Russell, D. C. Anderson, C. J. Epstein, S. Laroux, and D. N. Granger Modulation of P-selectin expression in the postischemic intestinal microvasculature Am J Physiol Gastrointest Liver Physiol, December 1, 1997; 273(6): G1326 - G1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. van den Eijnden-Schrauwen, D. E. Atsma, F. Lupu, R. E. M. de Vries, T. Kooistra, and J. J. Emeis Involvement of Calcium and G Proteins in the Acute Release of Tissue-Type Plasminogen Activator and von Willebrand Factor From Cultured Human Endothelial Cells Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2177 - 2187. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. E. Pedersen, B. S. Bochner, and B. J. Undem Cysteinyl Leukotrienes Induce P-Selectin Expression in Human Endothelial Cells via a Non-CysLT1 Receptor-Mediated Mechanism J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 655 - 662. [Abstract] [Full Text]
|
|
|
|
|
|
G. A. Barabino, R. J. Wise, V. A. Woodbury, B. Zhang, K. A. Bridges, R. P. Hebbel, J. Lawler, and B. M. Ewenstein Inhibition of Sickle Erythrocyte Adhesion to Immobilized Thrombospondin by von Willebrand Factor Under Dynamic Flow Conditions Blood, April 1, 1997; 89(7): 2560 - 2567. [Abstract] [Full Text] [PDF]
|
|