Article tools

Author information

Find articles by
Marcus, A. J. in:
JCI | PubMed | Google Scholar
Find articles by
Broekman, M. J. in:
JCI | PubMed | GoogleScholar

Published in Volume 66, Issue 5 (November,1980)
J. Clin. Invest. 66(5): 979-986 (1980). doi:10.1172/JCI109967.
Copyright © 1980, The American Society for Clinical Investigation

Articles

Synthesis of Prostacyclin from Platelet-derived Endoperoxides by Cultured Human Endothelial Cells

Aaron J. Marcus, Babette B. Weksler, Eric A. Jaffe and M. Johan Broekman

^{Divisions of Hematology-Oncology, Departments of Medicine, New York Veterans Administration Hospital, New York 10010} ^{Cornell University Medical College, New York 10021}

Published November, 1980

We have previously shown that aspirin-treated endothelial cells synthesize prostacyclin (PGI₂) from the purified prostaglandin endoperoxide PGH₂ (1978. J. Biol. Chem.253: 7138). To ascertain whether aspirin-treated endothelial cells produce PGI₂ from endoperoxides released by stimulated platelets, [³H]arachidonic acid-prelabeled platelets were reacted in aggregometer cuvettes with the calcium ionophore A 23187, thrombin, or collagen in the presence of aspirin-treated endothelial cell suspensions. This procedure permitted thin-layer radiochromatographic quantitation of [³H]PGI₂ as [³H]6-keto-PGF_1α and [³H]thromboxane A₂ (TXA₂) as [³H]TXB₂, as well as analysis of platelet aggregation responses in the same sample. In the presence of aspirin-treated endothelial cells, platelet aggregation in response to all three agents was inhibited. [³H]6-keto-PGF_1α was recovered from the supernates of the combined cell suspensions after stimulation by all three agents. The order of PGI₂ production initiated by the stimuli was ionophore > thrombin > collagen. The amounts of platelet [³H]TXB₂ recovered were markedly reduced by the addition of aspirin-treated endothelial cells. In separate experiments, 6-keto-PGF_1α and TXB₂ were quantitated by radioimmunoassay; the results paralleled those obtained with the use of radiolabeling. The quantity of 6-keto-PGF_1α measured by radioimmunoassay represented amounts of PGI₂ sufficient to inhibit platelet aggregation. These results were obtained when 200,000 platelets/μl were combined with 3,000-6,000 aspirin-treated endothelial cells/μl. At higher platelet levels the proportion of 6-keto-PGF_1α to TXB₂ decreased and platelet aggregation occurred. Control studies indicated that aspirin-treated endothelial cells could not synthesize PGI₂ from exogenous radioactive or endogenous arachidonate when stimulated with thrombin. Therefore the endothelial cell suspensions could only have used endoperoxides from stimulated platelets.

Thus, under our experimental conditions, production by endothelial cells of PGI₂ from endoperoxides derived from activated platelets could be demonstrated by two independent methods. These experimental conditions included: (a) enhanced platelet-endothelial cell proximity, as attainable in stirred cell suspensions; (b) use of increased endothelial cell/platelet ratios; and (c) utilization of arachidonate of high specific activity in radiolabeling experiments. Furthermore, when a mixture of platelets and endothelial cells that were not treated with aspirin was stimulated with thrombin, more than twice as much 6-keto-PGF_1α was formed than when endothelial cells were stimulated alone. These results indicate that endothelial cells can utilize platelet endoperoxides for PGI₂ formation to a significant extent.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Copying, redistribution, and other usage policies

Articles that cite this article:

Physiologic Functions of Normal Endothelial Cells
ERIC A. Jaffe
Ann N Y Acad Sci 454(1):279. doi:10.1111/j.1749-6632.1985.tb11868.x [CrossRef]

Blood Elements at Surfaces: Platelets
BARRY S. Coller
Ann N Y Acad Sci 516(1 blood in cont):362. doi:10.1111/j.1749-6632.1987.tb33056.x [CrossRef]

Arterial Endothelial Cell-derived Eicosanoids Alter Cholesterol Metabolism in Arterial Smooth Muscle Cells
DAVID P. Hajjar, AARON J. Marcus, KATHERINE A. Hajjar
Ann N Y Acad Sci 524(1 biology of th):411. doi:10.1111/j.1749-6632.1988.tb38571.x [CrossRef]

Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2
Tetsuya Hirabayashi, Toshihiko Murayama, Takao Shimizu
Biol Pharm Bull 27(8):1168. doi:10.1248/bpb.27.1168 [CrossRef]

Resistance to antiplatelet drugs: current status and future research
Udaya S Tantry, Kevin P Bliden, Paul A Gurbel
Expert Opin Pharmacother 6(12):2027. doi:10.1517/14656566.6.12.2027 [CrossRef]

THE INFLUENCE OF VITAMIN E ON HUMAN POLYMORPHONUCLEAR CELL METABOLISM AND FUNCTION
Robert L. Baehner, Laurence A. Boxer, Leah M. Ingraham, Charles Butterick, Richard A. Haak
Ann N Y Acad Sci 393(1 vitamin e):237. doi:10.1111/j.1749-6632.1982.tb31265.x [CrossRef]

Thrombin-induced increase in albumin permeability across the endothelium
Joe G. N. Garcia, Alma Siflinger-birnboim, Rena Bizios, Peter J. Del vecchio, John W. Fenton, Asrar B. Malik
J Cell Physiol 128(1):96. doi:10.1002/jcp.1041280115 [CrossRef]

Effects of sodium selenite on in vitro interactions between platelets and endothelial cells
M. M. Ricetti, G. C. Guidi, C. Tecchio, G. Bellisola, A. Rigo, G. Perona
IJ Clinical & Laboratory Research 29(2):80. doi:10.1007/s005990050068 [CrossRef]

Bidirectional modulation of platelet and polymorphonuclear leukocyte activities
A. Maschio, E. Dejana, G. Bazzoni
Ann Hematol 67(1):23. doi:10.1007/BF01709662 [CrossRef]

Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo
Jean-Etienne Fabre, Jennifer L. Goulet, Estelle Riche, MyTrang Nguyen, Kenneth Coggins, Steven Offenbacher, Beverly H. Koller
J Clin Invest 109(10):1373. doi:10.1172/JCI14869 [CrossRef]

Regulated formation of eicosanoids
F.A. Fitzpatrick, Roy Soberman
J Clin Invest 107(11):1347. doi:10.1172/JCI13241 [CrossRef]

Effects of isolation and culture on prostaglandin synthesis by porcine aortic endothelial and smooth muscle cells
Ann Ager, John L. Gordon, Salvador Moncada, Jeremy D. Pearson, John A. Salmon, Michael A. Trevethick
J Cell Physiol 110(1):9. doi:10.1002/jcp.1041100103 [CrossRef]

Effects of Unstimulated Polymorphonuclear Neutrophils on Porcine Distal Coronary Artery Tone.
Kuroda Satoshi, Abe Yukihiko, Maehara Kazuhira, Maruyama Yukio
Jpn Heart J 41(3):371. doi:10.1536/jhj.41.371 [CrossRef]

TxA2-mediated myocardial ischemia as a consequence of an acute lung inflammatory reaction in the rabbit
V. Evangelista, G. Dell'elba, A. Celardo, S. Manarini, C. Cerletti
J Thromb Haemost 1(2):314. doi:10.1046/j.1538-7836.2003.00067.x [CrossRef]

Heterologous cell-cell interactions: thromboregulation, cerebroprotection and cardioprotection by CD39 (NTPDase-1)
A. J. Marcus, M. J. Broekman, J. H. F. Drosopoulos, N. Islam, D. J. Pinsky, C. Sesti, R. Levi
J Thromb Haemost 1(12):2497. doi:10.1111/j.1538-7836.2003.00479.x [CrossRef]

Endothelial cells in culture produce a vasoconstrictor substance
Richard F. O'brien, Richard J. Robbins, Ivan F. Mcmurtry
J Cell Physiol 132(2):263. doi:10.1002/jcp.1041320210 [CrossRef]

Endothelial dysfunction in patients with polycythaemia vera
T. Neunteufl, S. Heher, T. Stefenelli, I. Pabinger, H. Gisslinger
Br J Haematol 115(2):354. doi:10.1046/j.1365-2141.2001.03092.x [CrossRef]

Critical role of the vascular endothelial cell in health and disease: a review article
Todd C. Duffy, Rebecca Kirby, Elke Rudloff
J Veter Emer Crit 14(2):84. doi:10.1111/j.1534-6935.2004.00116.x [CrossRef]

Human endothelial cells stimulate leukotriene synthesis and convert granulocyte released leukotriene A4 into leukotrienes B4, C4, D4 and E4
Hans-Erik Claesson, Jesper Haeggstrom
Eur J Biochem 173(1):93. doi:10.1111/j.1432-1033.1988.tb13971.x [CrossRef]

Prostaglandins, other eicosanoids and endothelial cells
K. SchrÃ¶r
Basic Res Cardiol 80(5):502. doi:10.1007/BF01907914 [CrossRef]

Aspirin Resistance
Costas Hanjis, William H. Frishman, Robert G. Lerner
Cardiol Rev 14(1):18. doi:10.1097/01.crd.0000148175.60718.69 [CrossRef]

S35b, a new phenylsulfonylfuroxan compound, inhibits thrombin-induced synthesis of platelet-activating factor and prostacyclin in human endothelial cells
R. Heller, F. Bussolino, R. Calvino, D. Ghigo, P. Alessio, R. Todde, R. Fruttero, G. Pescarmona, A. Gasco, U. Till
Agents Actions 40(3-4):157. doi:10.1007/BF01984055 [CrossRef]

Die Bedeutung des Endothels der Gefäßwand für die Aufrechterhaltung der Hämostase
U. Delvos, G. Müller-berghaus
Klin Wschr 63(24):1237. doi:10.1007/BF01738448 [CrossRef]

MATERNAL PLASMA PROSTACYCLIN CONCENTRATION IN PRE-ECLAMPSIA AND OTHER PREGNANCY COMPLICATIONS
O. Ylikorkala, P. Kirkinen, L. Viinikka
BJOG An Internal Journal of Obs Gyn 88(10):968. doi:10.1111/j.1471-0528.1981.tb01682.x [CrossRef]

Failure of Aspirin to Prevent Atherothrombosis
John W Eikelboom, Graeme J Hankey
Am J Cardiovasc Drugs 4(1):57. doi:10.2165/00129784-200404010-00006 [CrossRef]

Synthesis of Some Guanylhydrazones and Imidazolinylhydrazones as Thromboxane-Synthase and Platelet Aggregation Inhibitors
N. Desideri, I. Sestili, P. Piccardoni, S. Rotondo, C. Cerletti, M. L. Stein
Arch Pharm Pharm Med Chem 325(12):773. doi:10.1002/ardp.19923251206 [CrossRef]

Cell-Cell Interactions in the Eicosanoid Pathway
A. J. Marcus, L. B. Safier, H. L. Ullman, N. Islam, M.J Broekman, J. R. Falck, S. Fischer, C. v. Schacky
Ann N Y Acad Sci 516(1 blood in cont):407. doi:10.1111/j.1749-6632.1987.tb33059.x [CrossRef]

ARACHIDONIC ACID METABOLISM IN ENDOTHELIAL CELLS AND PLATELETS
A. J. Marcus, M. J. Broekman, B. B. Weksler, E. A. Jaffe, L. B. Safier, H. L. Ullman, N. Islam, K. Tack-goldman
Ann N Y Acad Sci 401(1 endothelium):195. doi:10.1111/j.1749-6632.1982.tb25718.x [CrossRef]

The Role of Leukotrienes in Human Pathophysiology
DONALD G. Raible, LAWRENCE M. Lichtenstein
Ann N Y Acad Sci 524(1 biology of th):334. doi:10.1111/j.1749-6632.1988.tb38556.x [CrossRef]

Effect of scavengers of active oxygen species and pretreatment with acetyl-salicylic acid on the injury to cultured endothelial cells by thrombin-stimulated platelets
Tor Larsen, Mona Berger Sørensen, Randi Olsen, Leif Jørgensen
In Vitro Cell Dev Biol 25(3):276. doi:10.1007/BF02628466 [CrossRef]

Thromboxane synthase inhibitors and receptor antagonists
Jos Vermylen, Hans Deckmyn
Cardiovasc Drugs Ther 6(1):29. doi:10.1007/BF00050914 [CrossRef]

CGS 22652: A New Potent Thromboxane A<sub>2</sub> Receptor Antagonist with Selective Thromboxane A<sub>2</sub> Synthase Inhibitory Properties
David S. Cohen, Donald N. Mcmartin, Michael P. Marietta, Patricia A. Zane, Rodney W. Lappe
Cardiovasc Drug Reviews 10(4):379. doi:10.1111/j.1527-3466.1992.tb00257.x [CrossRef]

Cardiovascular effects of valdecoxib: transducing human pharmacology results into clinical read-outs
Marta L Capone, Stefania Tacconelli, Luigia Di Francesco, Maria Petrelli, Paola Patrignani
eods 7(1):29. doi:10.1517/14740338.7.1.29 [CrossRef]

Nitric oxide modulation of transcellular biosynthesis of cys-leukotrienes in rabbit leukocyte-perfused heart
Carola Buccellati, Giuseppe Rossoni, Albino Bonazzi, Ferruccio Berti, Jacques Maclouf, Giancarlo Folco, Angelo Sala
Br J Pharmacol 120(6):1128. doi:10.1038/sj.bjp.0700994 [CrossRef]