Download PDF
Thromb Haemost 2001; 86(05): 1148-1155
DOI: 10.1055/s-0037-1616043
Review Article
Schattauer GmbH

Regulated Secretion in Endothelial Cells: Biology and Clinical Implications

Yvonne H. Datta
1   Division of Hematology/Oncology, Medical College of Wisconsin, USA
,
Bruce M. Ewenstein
2   Division of Hematology, Brigham & Women’s Hospital, Harvard Medical School, USA
› Author Affiliations
Further Information

Publication History

Received 09 March 2001

Accepted after revision 20 June 2001

Publication Date:
13 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Regulated secretion provides a means by which endothelial cells (EC) can rapidly and selectively alter the microenvironment of individual vascular beds, and modulate the interrelated processes of coagulation, fibrinolysis, and inflammation. The rapid release of high molecular weight multimers of von Willebrand factor (VWF) and surface expression of P-selectin in response to a wide variety of stimuli have been well documented, and are the result of exocytosis of Weibel-Palade bodies (WPB). The regulated release of other EC secretory proteins, including tissue plasminogen activator (tPA), interleukin-8, endothelin-1, and multimerin, has also been described. New light is being shed on how secretory proteins are selectively targeted to storage granules in EC, and on the molecular and cellular events that comprise regulated secretion. Knowledge of the mechanisms of sorting and secretion from EC storage granules may provide basis for new strategies for treating inflammatory and coagulation disorders.

Keywords

Endothelial cells - secretion - Weibel-Palade bodies - coagulation - inflammation
 

  • References

  • 1 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-90.
    CrossrefPubMedSearch in Google Scholar
  • 2 Ewenstein BM, Warhol MJ, Handin RI, Pober JS. Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells. J Cell Biol 1987; 104: 1423-33.
    CrossrefPubMedSearch in Google Scholar
  • 3 Federici AB, Bader R, Pagani S, Colibretti ML, De Marco L, Mannucci PM. Binding of von Willebrand factor to glycoproteins Ib and IIb/IIIa complex: affinity is related to multimeric size. Br J Haematol 1989; 73: 93-9.
    CrossrefPubMedSearch in Google Scholar
  • 4 Hattori R, Hamilton KK, Fugate RD, McEver RP, Sims PJ. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 1989; 264: 7768-71.
    PubMedSearch in Google Scholar
  • 5 Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 1989; 73: 1109-12.
    PubMedSearch in Google Scholar
  • 6 Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 1993; 74: 541-54.
    CrossrefPubMedSearch in Google Scholar
  • 7 Levine JD, Harlan JM, Harker LA, Joseph ML, Counts RB. Thrombin-mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture. Blood 1982; 60: 531-4.
    PubMedSearch in Google Scholar
  • 8 Datta YH, Romano M, Jacobson BC, Golan DE, Serhan CN, Ewenstein BM. Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation 1995; 92: 3304-11.
    CrossrefPubMedSearch in Google Scholar
  • 9 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-argi-nine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; 1: 869-72.
    PubMedSearch in Google Scholar
  • 10 Aird WC, Edelberg JM, Weiler-Guettler H, Simmons WW, Smith TW, Rosenberg RD. Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment. J Cell Biol 1997; 138: 1117-24.
    CrossrefPubMedSearch in Google Scholar
  • 11 Mohlke KL, Ginsburg D. von Willebrand disease and quantitative variation in von Willebrand factor. J Lab Clin Med 1997; 130: 252-61.
    CrossrefPubMedSearch in Google Scholar
  • 12 Wise RJ, Barr PJ, Wong PA, Kiefer MC, Brake AJ, Kaufman RJ. Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proc Natl Acad Sci USA 1990; 87: 9378-82.
    CrossrefPubMedSearch in Google Scholar
  • 13 Vischer UM, Wagner DD. von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. Blood 1994; 83: 3536-44.
    CrossrefPubMedSearch in Google Scholar
  • 14 Arvan P, Castle D. Sorting and storage during secretory granule biogenesis: looking backward and looking forward. Biochem J 1998; 332 (Suppl. 03) 593-610.
    CrossrefPubMedSearch in Google Scholar
  • 15 Halban PA, Irminger JC. Sorting and processing of secretory proteins. Biochem J 1994; 299 (Suppl. 01) 1-18.
    CrossrefPubMedSearch in Google Scholar
  • 16 Wagner DD, Saffaripour S, Bonfanti R, Sadler JE, Cramer EM, Chapman B, Mayadas TN. Induction of specific storage organelles by von Willebrand factor propolypeptide. Cell 1991; 64: 403-13.
    CrossrefPubMedSearch in Google Scholar
  • 17 Journet AM, Saffaripour S, Wagner DD. Requirement for both D domains of the propolypeptide in von Willebrand factor multimerization and storage. Thromb Haemost 1993; 70: 1053-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Journet AM, Saffaripour S, Cramer EM, Tenza D, Wagner DD. von Wille-brand factor storage requires intact prosequence cleavage site. Eur J Cell Biol 1993; 60: 31-41.
    PubMedSearch in Google Scholar
  • 19 Haberichter SL, Fahs SA, Montgomery RR. von Willebrand factor storage and multimerization: 2 independent intracellular processes. Blood 2000; 96: 1808-15.
    PubMedSearch in Google Scholar
  • 20 Mayadas TN, Wagner DD. Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly. Proc Natl Acad Sci USA 1992; 89: 3531-5.
    CrossrefPubMedSearch in Google Scholar
  • 21 Voorberg J, Fontijn R, Calafat J, Janssen H, Van Mourik JA, Pannekoek H. Biogenesis of von Willebrand factor-containing organelles in heterologous transfected CV-1 cells. EMBO J 1993; 12: 749-58.
    PubMedSearch in Google Scholar
  • 22 Montgomery RR, Jozwiak MA, Rosenberg JB, Nelson CA, Christopherson PA. Targeting of foreign protein expression in the endothelial secretory pathway using proteins linked to the propolypeptide of von Willebrand factor. Blood 1998; 92 (Suppl. 01) 708a.
    PubMedSearch in Google Scholar
  • 23 Cool DR, Normant E, Shen F, Chen HC, Pannell L, Zhang Y, Loh YP. Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell 1997; 88: 73-83.
    CrossrefPubMedSearch in Google Scholar
  • 24 Methia N, Denis CV, Wagner DD. Carboxypeptidase E does not mediate von Willebrand factor targeting to storage granules. Eur J Cell Biol 1999; 78: 884-91.
    CrossrefPubMedSearch in Google Scholar
  • 25 Koedam JA, Cramer EM, Briend E, Furie B, Furie BC, Wagner DD. P-selectin, a granule membrane protein of platelets and endothelial cells, follows the regulated secretory pathway in AtT-20 cells. J Cell Biol 1992; 116: 617-25.
    CrossrefPubMedSearch in Google Scholar
  • 26 Hop C, Guilliatt A, Daly M, de Leeuw HP, Brinkman HJ, Peake IR, VanMourik JA, Pannekoek H. Assembly of multimeric von Willebrand factordirects sorting of P- selectin. Arterioscler Thromb Vasc Biol 2000; 20: 1763-8.
    CrossrefPubMedSearch in Google Scholar
  • 27 Denis CV, Andre P, Saffaripour S, Wagner DD. Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand-factor-deficient mice. Proc Natl Acad Sci USA 2001; 987: 4072-7.
    PubMedSearch in Google Scholar
  • 28 Disdier M, Morrissey JH, Fugate RD, Bainton DF, McEver RP. Cytoplasmic domain of P-selectin (CD62) contains the signal for sortinginto the regulated secretory pathway. Mol Biol Cell 1992; 3: 309-21.
    CrossrefPubMedSearch in Google Scholar
  • 29 Chen D, Riesbeck K, McVey JH, Kemball-Cook G, Tuddenham EG, Lechler RI, Dorling A. Regulated inhibition of coagulation by porcine endothelial cells expressing P-selectin-tagged hirudin and tissue factor pathwayinhibitor fusion proteins. Transplantation 1999; 68: 832-9.
    CrossrefPubMedSearch in Google Scholar
  • 30 Fleming JC, Berger G, Guichard J, Cramer EM, Wagner DD. The transmembrane domain enhances granular targeting of P-selectin. Eur J Cell Biol 1998; 75: 1-43.
    CrossrefPubMedSearch in Google Scholar
  • 31 Hartwell DW, Mayadas TN, Berger G, Frenette PS, Rayburn H, Hynes RO, Wagner DD. Role of P-selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses. J Cell Biol 1998; 3: 1129-41.
    PubMedSearch in Google Scholar
  • 32 Wun TC, Capuano A. Initiation and regulation of fibrinolysis in human plasma at the plasminogen activator level. Blood 1987; 69: 1354-62.
    PubMedSearch in Google Scholar
  • 33 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93.
    CrossrefPubMedSearch in Google Scholar
  • 34 Emeis JJ, Eijnden-Schrauwen Y, van den Hoogen CM, de Priester W, Westmuckett A, Lupu F. An endothelial storage granule for tissue-type plasminogen activator. J Cell Biol 1997; 139: 245-56.
    CrossrefPubMedSearch in Google Scholar
  • 35 Schick BP, Gradowski JF, Antonio JD. Synthesis, secretion, and subcellular localization of serglycin proteoglycan in human endothelial cells. Blood 2001; 97: 449-58.
    CrossrefPubMedSearch in Google Scholar
  • 36 Datta YH, Youssoufian H, Marks PW, Ewenstein BM. Targeting of a heterologous protein to a regulated secretion pathway in cultured endothelial cells. Blood 1999; 94: 2696-703.
    PubMedSearch in Google Scholar
  • 37 Rosnoblet C, Vischer UM, Gerard RD, Irminger JC, Halban PA, Kruithof EK. Storage of tissue-type plasminogen activator in Weibel-Palade bodies of human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 1796-803.
    CrossrefPubMedSearch in Google Scholar
  • 38 Rosnoblet C, Ribba AS, Wollheim CB, Kruithof EK, Vischer UM. Regulated von Willebrand factor (vWf) secretion is restored by pro-vWf expression in a transfectable endothelial cell line. Biochim Biophys Acta 2000; 1495: 112-9.
    CrossrefPubMedSearch in Google Scholar
  • 39 Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of micro-vascular endothelial cells. J Exp Med 1998; 188: 1751-6.
    CrossrefPubMedSearch in Google Scholar
  • 40 Wolff B, Burns AR, Middleton J, Rot A. Endothelial cell “memory” of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies. J Exp Med 1998; 188: 1757-62.
    CrossrefPubMedSearch in Google Scholar
  • 41 Anrather D, Millan MT, Palmetshofer A, Robson SC, Geczy C, Ritchie AJ, Bach FH, Ewenstein BM. Thrombin activates nuclear factor-kappaB and potentiates endothelial cell activation by TNF. J Immunol 1997; 159: 5620-8.
    PubMedSearch in Google Scholar
  • 42 Schini VB, Hendrickson H, Heublein DM, Burnett Jr. JC, Vanhoutte PM. Thrombin enhances the release of endothelin from cultured porcine aortic endothelial cells. Eur J Pharmacol 1989; 165: 333-4.
    CrossrefPubMedSearch in Google Scholar
  • 43 Emori T, Hirata Y, Ohta K, Shichiri M, Marumo F. Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun 1989; 160: 93-100.
    CrossrefPubMedSearch in Google Scholar
  • 44 Russell FD, Skepper JN, Davenport AP. Evidence using immunoelectron microscopy for regulated and constitutive pathways in the transport and release of endothelin. J Cardiovasc Pharmacol 1998; 31: 424-30.
    CrossrefPubMedSearch in Google Scholar
  • 45 Macarthur H, Warner TD, Wood EG, Corder R, Vane JR. Endothelin-1 release from endothelial cells in culture is elevated both acutely and chronically by short periods of mechanical stretch. Biochem Biophys Res Commun 1994; 200: 395-400.
    CrossrefPubMedSearch in Google Scholar
  • 46 Russell FD, Skepper JN, Davenport AP. Human endothelial cell storage granules: a novel intracellular site for isoforms of the endothelin-converting enzyme. Circ Res 1998; 83: 314-21.
    CrossrefPubMedSearch in Google Scholar
  • 47 Harrison VJ, Barnes K, Turner AJ, Wood E, Corder R, Vane JR. Identification of endothelin 1 and big endothelin 1 in secretory vesicles isolated from bovine aortic endothelial cells. Proc Natl Acad Sci USA 1995; 92: 6344-8.
    CrossrefPubMedSearch in Google Scholar
  • 48 Vischer UM, Wagner DD. CD63 is a component of Weibel-Palade bodies of human endothelial cells. Blood 1993; 82: 1184-91.
    PubMedSearch in Google Scholar
  • 49 Subramaniam M, Koedam JA, Wagner DD. Divergent fates of P-selectin and E-selectin after their expression on the plasma membrane. Mol Biol Cell 1993; 4: 791-801.
    CrossrefPubMedSearch in Google Scholar
  • 50 Kobayashi T, Vischer UM, Rosnoblet C, Lebrand C, Lindsay M, Parton RG, Kruithof EK, Gruenberg J. The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Mol Biol Cell 2000; 11: 1829-43.
    CrossrefPubMedSearch in Google Scholar
  • 51 Schnyder-Candrian S, Borsig L, Moser R, Berger EG. Localization of alpha 1,3-fucosyltransferase VI in Weibel-Palade bodies of human endothelial cells. Proc Natl Acad Sci USA 2000; 97: 8369-74.
    CrossrefPubMedSearch in Google Scholar
  • 52 Hayward CP, Cramer EM, Song Z, Zheng S, Fung R, Masse JM, Stead RH, Podor TJ. Studies of multimerin in human endothelial cells. Blood 1998; 91: 1304-17.
    PubMedSearch in Google Scholar
  • 53 Lupu C, Lupu F, Dennehy U, Kakkar VV, Scully MF. Thrombin induces the redistribution and acute release of tissue factor pathway inhibitor from specific granules within human endothelial cells in culture. Arterioscler Thromb Vasc Biol 1995; 15: 2055-62.
    CrossrefPubMedSearch in Google Scholar
  • 54 Stern D, Brett J, Harris K, Nawroth P. Participation of endothelial cells in the protein C-protein S anticoagulant pathway: the synthesis and release of protein S. J Cell Biol 1986; 102: 1971-8.
    CrossrefPubMedSearch in Google Scholar
  • 55 Hayward CP, Warkentin TE, Horsewood P, Kelton JG. Multimerin: a series of large disulfide-linked multimeric proteins within platelets. Blood 1991; 77: 2556-60.
    PubMedSearch in Google Scholar
  • 56 Hayward CP, Furmaniak-Kazmierczak E, Cieutat AM, Moore JC, Bainton DF, Nesheim ME, Kelton JG, Cote G. Factor V is complexed with multimerin in resting platelet lysates and colocalizes with multimerin in platelet alpha-granules. J Biol Chem 1995; 270: 19217-24.
    CrossrefPubMedSearch in Google Scholar
  • 57 Lupu C, Kruithof EK, Kakkar VV, Lupu F. Acute release of tissue factor pathway inhibitor after in vivo thrombin generation in baboons. Thromb Haemost 1999; 82: 1652-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 58 Brett JG, Steinberg SF, deGroot PG, Nawroth PP, Stern DM. Norepinephrine down-regulates the activity of protein S on endothelial cells. J Cell Biol 1988; 106: 2109-18.
    CrossrefPubMedSearch in Google Scholar
  • 59 Shen FS, Loh YP. Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth hormone in cpefat mice associated with a carboxypeptidase E mutation. Proc Natl Acad Sci USA 1997; 94: 5314-19.
    CrossrefPubMedSearch in Google Scholar
  • 60 Rosenberg JB, Foster PA, Kaufman RJ, Vokac EA, Moussalli M, Kroner PA, Montgomery RR. Intracellular trafficking of factor VIII to von Wille-brand factor storage granules. J Clin Invest 1998; 101: 613-24.
    CrossrefPubMedSearch in Google Scholar
  • 61 Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997; 90: 2515-21.
    PubMedSearch in Google Scholar
  • 62 Hattori R, Hamilton KK, McEver RP, Sims PJ. Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J Biol Chem 1989; 264: 9053-60.
    PubMedSearch in Google Scholar
  • 63 Birch KA, Ewenstein BM, Golan DE, Pober JS. Prolonged peak elevations in cytoplasmic free calcium ions, derived from intracellular stores, correlate with the extent of thrombin- stimulated exocytosis in single human umbilical vein endothelial cells. J Cell Physiol 1994; 160: 545-54.
    CrossrefPubMedSearch in Google Scholar
  • 64 Pinsky DJ, Naka Y, Liao H, Oz MC, Wagner DD, Mayadas TN, Johnson RC, Hynes RO, Heath M, Lawson CA, Stern DM. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97: 493-500.
    CrossrefPubMedSearch in Google Scholar
  • 65 Moffat EH, Giddings JC, Bloom AL. The effect of desamino-D-arginine vasopressin (DDAVP) and naloxone infusions on factor VIII and possible endothelial cell (EC) related activities. Br J Haematol 1984; 57: 651-62.
    CrossrefPubMedSearch in Google Scholar
  • 66 Barnhart MI, Chen S, Lusher JM. DDAVP: does the drug have a direct effect on the vessel wall?. Thromb Res 1983; 31: 239-53.
    CrossrefPubMedSearch in Google Scholar
  • 67 Hashemi S, Palmer DS, Aye MT, Ganz PR. Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from endothelial cells. J Cell Physiol 1993; 154: 496-505.
    CrossrefPubMedSearch in Google Scholar
  • 68 Kaufmann JE, Oksche A, Wollheim CB, Gunther G, Rosenthal W, Vischer UM. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest 2000; 106: 107-16.
    CrossrefPubMedSearch in Google Scholar
  • 69 Birch KA, Pober JS, Zavoico GB, Means AR, Ewenstein BM. Calcium/calmodulin transduces thrombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothelial cells. J Cell Biol 1992; 118: 1501-10.
    CrossrefPubMedSearch in Google Scholar
  • 70 Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature 1991; 353: 674-7.
    CrossrefPubMedSearch in Google Scholar
  • 71 Jaffe EA, Grulich J, Weksler BB, Hampel G, Watanabe K. Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells. J Biol Chem 1987; 262: 8557-65.
    PubMedSearch in Google Scholar
  • 72 Brock TA, Capasso EA. Thrombin and histamine activate phospholipase C in human endothelial cells via a phorbol ester-sensitive pathway. J Cell Physiol 1988; 136: 54-62.
    CrossrefPubMedSearch in Google Scholar
  • 73 Vischer UM, Wollheim CB. Epinephrine induces von Willebrand factor release from cultured endothelial cells: involvement of cyclic AMP-dependent signalling in exocytosis. Thromb Haemost 1997; 77: 1182-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 74 Vischer UM, Wollheim CB. Purine nucleotides induce regulated secretion of von Willebrand factor: involvement of cytosolic Ca2+ and cyclic adenosine monophosphate-dependent signaling in endothelial exocytosis. Blood 1998; 91: 118-27.
    PubMedSearch in Google Scholar
  • 75 Tranquille N, Emeis JJ. The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor. Thromb Haemost 1993; 69: 259-61.
    Thieme ConnectPubMedSearch in Google Scholar
  • 76 Vischer UM, Barth H, Wollheim CB. Regulated von Willebrand factor secretion is associated with agonist-specific patterns of cytoskeletal remodeling in cultured endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 883-91.
    CrossrefPubMedSearch in Google Scholar
  • 77 de Leeuw HP, Wijers-Koster PM, Van Mourik JA, Voorberg J. Small GTP-binding protein RalA associates with Weibel-Palade bodies in endothelial cells. Thromb Haemost 1999; 82: 1177-81.
    Thieme ConnectPubMedSearch in Google Scholar
  • 78 Volknandt W, Pevsner J, Elferink LA, Scheller RH. Association of three small GTP-binding proteins with cholinergic synaptic vesicles. FEBS Lett 1993; 317: 53-6.
    CrossrefPubMedSearch in Google Scholar
  • 79 Mark BL, Jilkina O, Bhullar RP. Association of Ral GTP-binding protein with human platelet dense granules. Biochem Biophys Res Commun 1996; 225: 40-6.
    CrossrefPubMedSearch in Google Scholar
  • 80 Wang KL, Khan MT, Roufogalis BD. Identification and characterization of a calmodulin-binding domain in Ral-A, a Ras-related GTP-binding protein purified from human erythrocyte membrane. J Biol Chem 1997; 272: 16002-9.
    CrossrefPubMedSearch in Google Scholar
  • 81 McShea A, Datta YH, Ewenstein BM, Golan DE, Bach FH, Wrighton CJ. Infection by replication-deficient adenovirus vectors potentiates regulated secretion in HUVEC: Mechanism and implications for adenovirus-mediated gene therapy. Blood 1985; 86: 1002a.
    PubMedSearch in Google Scholar
  • 82 Konig J, Prenen J, Nilius B, Gerke V. The annexin II-p11 complex is involved in regulated exocytosis in bovine pulmonary artery endothelial cells. J Biol Chem 1998; 273: 19679-84.
    CrossrefPubMedSearch in Google Scholar
  • 83 Buul-Wortelboer MF, Brinkman HJ, Reinders JH, van Aken WG, Van Mourik JA. Polar secretion of von Willebrand factor by endothelial cells. Biochim Biophys Acta 1989; 1011: 129-33.
    CrossrefPubMedSearch in Google Scholar
  • 84 Sporn LA, Marder VJ, Wagner DD. Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells. J Cell Biol 1989; 108: 1283-9.
    CrossrefPubMedSearch in Google Scholar
  • 85 Kaul DK, Tsai HM, Liu XD, Nakada MT, Nagel RL, Coller BS. Monoclonal antibodies to alphaVbeta3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood 2000; 95: 368-74.
    PubMedSearch in Google Scholar
  • 86 Richardson M, Tinlin S, De Reske M, Webster S, Senis Y, Giles AR. Morphological alterations in endothelial cells associated with the release of von Willebrand factor after thrombin generation in vivo. Arterioscler Thromb 1994; 14: 990-9.
    CrossrefPubMedSearch in Google Scholar
  • 87 Reinders JH, Vervoorn RC, Verweij CL, Van Mourik JA, De Groot PG. Perturbation of cultured human vascular endothelial cells by phorbol ester or thrombin alters the cellular von Willebrand factor distribution. J Cell Physiol 1987; 133: 79-87.
    CrossrefPubMedSearch in Google Scholar
  • 88 Jansson JH, Nilsson TK, Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66: 351-5.
    CrossrefPubMedSearch in Google Scholar
  • 89 Dong ZM, Brown AA, Wagner DD. Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice. Circulation 2000; 101: 2290-5.
    CrossrefPubMedSearch in Google Scholar
  • 90 Hamilton KK, Sims PJ. Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1. J Clin Invest 1987; 79: 600-8.
    CrossrefPubMedSearch in Google Scholar
  • 91 Marcus AJ, Safier LB. Thromboregulation: multicellular modulation of platelet reactivity in hemostasis and thrombosis. FASEB J 1993; 7: 516-22.
    CrossrefPubMedSearch in Google Scholar
  • 92 Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
    PubMedSearch in Google Scholar
  • 93 Langer F, Morys-Wormann C, Kusers B, Storck J. Endothelial protease-activated receptor-2 induces tissue factor expression and von Willebrand factor release. Br J Haematol 1999; 105: 543-50.
    PubMedSearch in Google Scholar