|
|
 Previous Article | Table of Contents | Next Article 
Thrombopoietin primes human platelet aggregation induced by shear stress
and by multiple agonists
A Oda, Y Miyakawa, BJ Druker, K Ozaki, K Yabusaki, Y Shirasawa, M Handa, T Kato, H Miyazaki, A Shimosaka and Y Ikeda
Division of Hematology, Department of Internal Medicine, Keio University,
Tokyo, Japan.
Recombinant thrombopoietin has been reported to stimulate
megakaryocytopoiesis and thrombopoiesis and it may be quite useful to treat
patients with low platelet counts after chemotherapy. As little is known
regarding the possible activation of platelets by thrombopoietin, we
examined the effects of thrombopoietin on platelet aggregation induced by
shear stress and various agonists in native plasma. Using hirudin as an
anticoagulant, thrombopoietin (1 to 100 ng/mL) enhanced platelet
aggregation induced by 2 micromol/L adenosine- diphosphate (ADP) in a dose
dependent fashion. The enhancement was not affected by treatment of
platelets with 1 mmol/L aspirin plus SQ-29548 (a thromboxane antagonist, 1
micromol/L) but was inhibited by a soluble form of the thrombopoietin
receptor, suggesting that the enhancement was mediated by the specific
receptors and does not require thromboxane production. Epinephrine (1
micromol/L), which does not induce platelet aggregation in hirudin platelet
rich plasma (PRP), did so in the presence of thrombopoietin (10 ng/mL).
Thrombopoietin (10 ng/mL) also enhanced or primed platelet aggregation
induced by collagen (0.5 micron.mL),. thrombin, serotonin, and vasopressin.
Thrombopoietin does not induce any rise in cytosolic ionized calcium
concentration nor activation of protein kinase C, as estimated by
phosphorylation of preckstrin, indicating that the priming effects of
thrombopoietin does not require those processes. The ADP- or
thrombin-induced rise in cytosolic ionized calcium concentration was not
enhanced by thrombopoietin (100 ng/mL). Further, shear (ca. 90
dyn/cm2)-induced platelet aggregation was also potentiated by
thrombopoietin. The priming effect on epinephrine-induced platelet
aggregation in hirudin PRP was unique to thrombopoietin, with no effects
seen using interleukin-6 (IL-6), IL-11, IL-3, erythropoietin,
granulocyte-colony stimulating factor, granulocyte macrophage-colony
stimulating factor, or c-kit ligand. These data indicate that monitoring of
platelet functions may be necessary in the clinical trials of
thrombopoietin.
Volume 87,
Issue 11,
pp. 4664-4670,
06/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Gernsheimer
Chronic Idiopathic Thrombocytopenic Purpura: Mechanisms of Pathogenesis
Oncologist,
January 1, 2009;
14(1):
12 - 21.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Nogami, H. Yoshida, K. Koizumi, H. Yamada, K. Abe, A. Arimura, N. Yamane, K. Takahashi, A. Yamane, A. Oda, et al.
The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis
Haematologica,
October 1, 2008;
93(10):
1495 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dordelmann, R. Telgmann, E. Brand, C. Hagedorn, B. Schroer, S. Hasenkamp, P. Baumgart, P. Kleine-Katthofer, M. Paul, and S.-M. Brand-Herrmann
Functional and Structural Profiling of the Human Thrombopoietin Gene Promoter
J. Biol. Chem.,
September 5, 2008;
283(36):
24382 - 24391.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. B. Gernsheimer
The Pathophysiology of ITP Revisited: Ineffective Thrombopoiesis and the Emerging Role of Thrombopoietin Receptor Agonists in the Management of Chronic Immune Thrombocytopenic Purpura
Hematology,
January 1, 2008;
2008(1):
219 - 226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lupia, O. Bosco, S. Bergerone, A. E. Dondi, A. Goffi, E. Oliaro, M. Cordero, L. Del Sorbo, G. Trevi, and G. Montrucchio
Thrombopoietin Contributes to Enhanced Platelet Activation in Patients With Unstable Angina
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2195 - 2203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Campus, P. Lova, A. Bertoni, F. Sinigaglia, C. Balduini, and M. Torti
Thrombopoietin Complements Gi- but Not Gq-dependent Pathways for Integrin {alpha}IIb{beta}3 Activation and Platelet Aggregation
J. Biol. Chem.,
July 1, 2005;
280(26):
24386 - 24395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Konstantinides, K. Schafer, J. G. Neels, C. Dellas, and D. J. Loskutoff
Inhibition of Endogenous Leptin Protects Mice From Arterial and Venous Thrombosis
Arterioscler Thromb Vasc Biol,
November 1, 2004;
24(11):
2196 - 2201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kirito, M. Osawa, H. Morita, R. Shimizu, M. Yamamoto, A. Oda, H. Fujita, M. Tanaka, K. Nakajima, Y. Miura, et al.
A functional role of Stat3 in in vivo megakaryopoiesis
Blood,
May 1, 2002;
99(9):
3220 - 3227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Hechler, P. Toselli, C. Ravanat, C. Gachet, and K. Ravid
Mpl Ligand Increases P2Y1 Receptor Gene Expression in Megakaryocytes with No Concomitant Change in Platelet Response to ADP
Mol. Pharmacol.,
November 1, 2001;
60(5):
1112 - 1120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-m. Pasquet, B. S. Gross, M.-P. Gratacap, L. Quek, S. Pasquet, B. Payrastre, G. van Willigen, J. C. Mountford, and S. P. Watson
Thrombopoietin potentiates collagen receptor signaling in platelets through a phosphatidylinositol 3-kinase-dependent pathway
Blood,
June 1, 2000;
95(11):
3429 - 3434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Oda, Y. Ikeda, H. D. Ochs, B. J. Druker, K. Ozaki, M. Handa, T. Ariga, Y. Sakiyama, O. N. Witte, and M. I. Wahl
Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking
Blood,
March 1, 2000;
95(5):
1663 - 1670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-M. Luoh, E. Stefanich, G. Solar, H. Steinmetz, T. Lipari, T. I. Pestina, C. W. Jackson, and F. J. de Sauvage
Role of the Distal Half of the c-Mpl Intracellular Domain in Control of Platelet Production by Thrombopoietin In Vivo
Mol. Cell. Biol.,
January 15, 2000;
20(2):
507 - 515.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. Archimbaud, O. G. Ottmann, J. A. L. Yin, K. Lechner, H. Dombret, M. A. Sanz, G. Heil, P. Fenaux, W. Brugger, A. Barge, et al.
A Randomized, Double-Blind, Placebo-Controlled Study With Pegylated Recombinant Human Megakaryocyte Growth and Development Factor (PEG-rHuMGDF) as an Adjunct to Chemotherapy for Adults With De Novo Acute Myeloid Leukemia
Blood,
December 1, 1999;
94(11):
3694 - 3701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-C. Yang, K. Tsuji, A. Oda, Y. Ebihara, M.-j. Xu, A. Kaneko, S. Hanada, T. Mitsui, A. Kikuchi, A. Manabe, et al.
Differential Effects of Human Granulocyte Colony-Stimulating Factor (hG-CSF) and Thrombopoietin on Megakaryopoiesis and Platelet Function in hG-CSF Receptor-Transgenic Mice
Blood,
August 1, 1999;
94(3):
950 - 958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ozaki, A. Oda, H. Wakao, J. Rhodes, B. J. Druker, A. Ishida, M. Wakui, S. Okamoto, K. Morita, M. Handa, et al.
Thrombopoietin Induces Association of Crkl With STAT5 But Not STAT3 in Human Platelets
Blood,
December 15, 1998;
92(12):
4652 - 4662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kaplan, S. Kaplan, K. F. Marcoe, L. R. Sauvage, and W. P. Hammond
The Effect of Hematopoietic Growth Factors on Platelet Aggregability
Clinical and Applied Thrombosis/Hemostasis,
October 1, 1998;
4(4):
238 - 242.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Bunting, R. Widmer, T. Lipari, L. Rangell, H. Steinmetz, K. Carver-Moore, M. W. Moore, G.-A. Keller, and F. J. de Sauvage
Normal Platelets and Megakaryocytes Are Produced In Vivo in the Absence of Thrombopoietin
Blood,
November 1, 1997;
90(9):
3423 - 3429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Abraham and R. L. Basser
Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies
Oncologist,
October 1, 1997;
2(5):
311 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kato, A. Oda, Y. Inagaki, H. Ohashi, A. Matsumoto, K. Ozaki, Y. Miyakawa, H. Watarai, K. Fuju, A. Kokubo, et al.
Thrombin cleaves recombinant human thrombopoietin: One of the proteolytic events that generates truncated forms of thrombopoietin
PNAS,
April 29, 1997;
94(9):
4669 - 4674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Miyakawa, A. Oda, B. J. Druker, K. Ozaki, M. Handa, H. Ohashi, and Y. Ikeda
Thrombopoietin and Thrombin Induce Tyrosine Phosphorylation of Vav in Human Blood Platelets
Blood,
April 15, 1997;
89(8):
2789 - 2798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
