Platelet membrane glycoprotein abnormalities in patients with myeloproliferative disorders and secondary thrombocytosis

Clézardin, Philippe; McGregor, John L.; Dechavanne, M; Clemetson, Kenneth J.

doi:10.1111/j.1365-2141.1985.tb07419.x

Cited by 67 publications

(27 citation statements)

References 25 publications

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“…In addition, injection of neuraminidases into mammals also reduces the half-life of the platelets (10,19). More importantly, cell surface sialylation is physiologically decreased in several human diseases, resulting in faster removal of platelets from the blood (1,11,17,28). These findings clearly indicate that sialic acid residues are involved in the platelet half-life in blood.…”

mentioning

confidence: 57%

The trans -Sialidase from Trypanosoma cruzi Induces Thrombocytopenia during Acute Chagas' Disease by Reducing the Platelet Sialic Acid Contents

et al. 2005

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Strong thrombocytopenia is observed during acute infection with Trypanosoma cruzi, the parasitic protozoan agent of American trypanosomiasis or Chagas' disease. The parasite sheds trans-sialidase, an enzyme able to mobilize the sialyl residues on cell surfaces, which is distributed in blood and is a virulence factor. Since the sialic acid content on the platelet surface is crucial for determining the half-life of platelets in blood, we examined the possible involvement of the parasite-derived enzyme in thrombocytopenia induction. We found that a single intravenous injection of trans-sialidase into naïve mice reduced the platelet count by 50%, a transient effect that lasted as long as the enzyme remained in the blood. CD43؊/؊ mice were affected to a similar extent. When green fluorescent protein-expressing platelets were treated in vitro with trans-sialidase, their sialic acid content was reduced together with their life span, as determined after transfusion into naïve animals. No apparent deleterious effect on the bone marrow was observed. A central role for Kupffer cells in the clearance of trans-sialidase-altered platelets was revealed after phagocyte depletion by administration of clodronate-containing liposomes and splenectomy. Consistent with this, parasite strains known to exhibit more trans-sialidase activity induced heavier thrombocytopenia. Finally, the passive transfer of a trans-sialidaseneutralizing monoclonal antibody to infected animals prevented the clearance of transfused platelets. Results reported here strongly support the hypothesis that the trans-sialidase is the virulence factor that, after depleting the sialic acid content of platelets, induces the accelerated clearance of the platelets that leads to the thrombocytopenia observed during acute Chagas' disease.

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mentioning

confidence: 57%

The trans -Sialidase from Trypanosoma cruzi Induces Thrombocytopenia during Acute Chagas' Disease by Reducing the Platelet Sialic Acid Contents

et al. 2005

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“…Thrombospondins secreted from thrombin-stimulated platelets and into the culture medium of human endothelial cells and fibroblasts were purified by a modification of the methods of Lawler et al [9] and Clezardin et al [32]. Briefly the culture medium (50-100 ml) from both endothelial cells and fibroblasts or the supernatant (15-30 ml) from thrombin-stimulated platelets were loaded onto a heparinSepharose column (120 x 20 mm) equilibrated in 20 mM Tris buffer, pH 7.4, containing 0.35 M NaCl (buffer A).…”

Section: Purijkation Of Human Thrombospondins From Platelets Endothementioning

confidence: 99%

Structural and immunological comparison of human thrombospondins isolated from platelets and from culture supernatants of endothelial cells and fibroblasts

Clézardin

Hunter

Lawler

et al. 1986

European Journal of Biochemistry

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Thrombospondin is a 450-kDa glycoprotein secreted by a variety of cells including endothelial cells, fibroblasts and platelets. The aim of this study was to compare the structural and immunological properties of human endothelial, fibroblast and platelet thrombospondins. All three thrombospondins were purified, digested with thermolysin, and the subsequent thermolysin-generated fragments isolated on a Superose 12 gel-permeation column using non-denaturating conditions. Each isolated proteolytic fragment of thrombospondins was then detected using either a radioimmunoassay with a polyclonal antibody or an enzyme-linked immunosorbent assay with three monoclonal antibodies (P10, MA-I, MA-11) directed against different epitopes of whole platelet thrombospondin. The fragmentation pattern of human endothelial thrombospondin consists of six major thermolysin-generated fragments (1 35 -110, 98 -82, 54 -47, 25 -20, 18 -15 and 10 kDa) having molecular masses very similar to those observed with human fibroblast thrombospondin (1 15 -100, 92 -80, 54 -49, 27 -21, 17-13 and 12-10 kDa). Treatment of platelet thrombospondin with thermolysin only generated four proteolytic fragments having molecular masses of 110, 50, 25 and 12/10 kDa respectively. All these proteolytic fragments of endothelial, fibroblast and platelet thrombospondins were recognized by a 'polyclonal antibody. Monoclonal antibodies MA-I and P10 essentially recognized two proteolytic fragments (135 -110;98 -82 kDa) of endothelial and fibroblast (1 15 -100, 92-80 kDa) thrombospondins, and the 110-kDa fragment of platelet thrombospondin. Monoclonal antibody MA-I1 recognized three proteolytic fragments (54 -47, 25 -20, 18 -15 kDa) of endothelial and fibroblast (54-49, 27-21, 17-13 kDa) thrombospondins, and two fragments (50, 25 kDa) of platelet thrombospondin, different from those detected by P10 an MA-I. The results clearly demonstrate that, under non-denaturating conditions, endothelial and fibroblast thrombospondins are structurally different from platelet thrombospondin since two fragments of endothelial thrombospondin (98 -82, 18 -15 kDa), equivalent to those of fibroblast thrombospondin (92-80, 17-13 kDa), are not released from platelet thrombospondin after thermolysin treatment. These three forms of thrombospondin are, however, immunologically indistinguishable. To investigate further the structural differences observed between platelet and the two other forms of thrombospondin, their degree of polymerization was compared. Prior to thermolysin treatment, the three forms of thrombospondin were separated into several oligomers ranging from 450 kDa to 3300 kDa when injected onto a Superose 6 gel-permeation column. In the presence of thermolysin, platelet thrombospondin oligomers were all digested whereas the 3300 kDa oligomer of endothelial or fibroblast thrombospondin was unaffected. All these oligomers were recognized by a polyclonal antibody and three monoclonal antibodies directed against platelet thrombospondin. Such a resistance to proteolysis of endothelia...

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“…In contrast, the definition of acquired disorders of platelet membrane glycoproteins has been less clear (2)(3)(4)(5)(6)(7). Changes ofsurface glycoproteins may occur in circulating platelets that could increase the risk for bleeding or thrombosis: plasma membrane microparticles can be lost, causing a decreased concentration of intrinsic plasma membrane glycoproteins (8)(9)(10)(11)(12); the microparticles themselves may accumulate in the plasma; a-granule membrane proteins can become exposed on the platelet surface following secretion (13)(14)(15); and large, contact-promoting a-granule secreted proteins can rebind to the cell surface (16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.

George¹,

Pickett²,

Saucerman³

et al. 1986

J. Clin. Invest.

451

164

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The accurate definition of surface glycoprotein abnormalities in circulating platelets may provide better understanding of bleeding and thrombotic disorders. Platelet surface glycoproteins were measured on intact platelets in whole blood and platelet membrane microparticles were assayed in cell-free plasma using 125I-monoclonal antibodies. The glycoproteins (GP) studied were: GP lb and GP Ilb-Illa, two of the major intrinsic plasma membrane glycoproteins; GMP-140, an a-granule membrane glycoprotein that becomes exposed on the platelet surface following secretion; and thrombospondin (TSP), an a-granule secreted glycoprotein that rebinds to the platelet surface. Thrombin-induced secretion in normal platelets caused the appearance of GMP-140 and TSP on the platelet surface, increased exposure of GP Ilb-Illa, and decreased antibody binding to GP lb. Patients with adult respiratory distress syndrome had an increased concentration of GMP-140 and TSP on the surface of their platelets, demonstrating in vivo platelet secretion, but had no increase of platelet microparticles in their plasma. In contrast, patients after cardiac surgery with cardiopulmonary bypass demonstrated changes consistent with membrane fragmentation without secretion: a decreased platelet surface concentration of GP lb and GP 1Ib with no increase of GMP-140 and TSP, and an increased plasma concentration of platelet membrane microparticles. These methods will help to define acquired abnormalities of platelet surface glycoproteins.

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Platelet membrane glycoprotein abnormalities in patients with myeloproliferative disorders and secondary thrombocytosis

Cited by 67 publications

References 25 publications

The trans -Sialidase from Trypanosoma cruzi Induces Thrombocytopenia during Acute Chagas' Disease by Reducing the Platelet Sialic Acid Contents

The trans -Sialidase from Trypanosoma cruzi Induces Thrombocytopenia during Acute Chagas' Disease by Reducing the Platelet Sialic Acid Contents

Structural and immunological comparison of human thrombospondins isolated from platelets and from culture supernatants of endothelial cells and fibroblasts

Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.

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