scholarly journals Monocytes and platelets share the glycoproteins IIb and IIIa that are absent from both cells in Glanzmann's thrombasthenia type I

1983 ◽  
Vol 214 (2) ◽  
pp. 331-337 ◽  
Author(s):  
G Gogstad ◽  
Ø Hetland ◽  
N O Solum ◽  
H Prydz
Keyword(s):  
Platelet Membrane ◽  
Type I ◽  
Membrane Glycoproteins ◽  
Edta Treatment ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia

By means of an antiserum specific to the complex of the platelet membrane glycoproteins IIb and IIIa we demonstrate here that monocytes and purified monocyte membranes share these glycoproteins with platelets. The monocyte glycoprotein IIb-IIIa complex showed complete immunological identity with the platelet counterpart and, furthermore, dissociated after EDTA treatment exactly as did the platelet complex. In Glanzmann's thrombasthenia type I, monocytes as well as platelets lack this antigen completely.

scholarly journals Residual amounts of glycoproteins IIb and IIIa may be present in the platelets of most patients with Glanzmann's thrombasthenia

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 1021-1024 ◽  
Author(s):  
AT Nurden ◽  
D Didry ◽  
N Kieffer ◽  
RP McEver
Keyword(s):  
Bleeding Disorder ◽  
Platelet Membrane ◽  
Type I ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Polyclonal Rabbit ◽  
Glanzmann's Thrombasthenia ◽  
Genes Encoding ◽  
Or Genes

Abstract Glanzmann's thrombasthenia is an inherited bleeding disorder characterized by abnormalities of platelet membrane glycoproteins (GP) IIb and IIIa. Most patients, usually designated as type I, have been reported to have undetectable levels of GP IIb and GP IIIa with the assay used. We have used polyclonal rabbit antibodies against GP IIb and GP IIIa in a sensitive immunoblot procedure capable of revealing trace amounts of these glycoproteins. Platelets from nine thrombasthenic patients, including seven with type I disease, were studied. GP IIIa, although decreased, was clearly detectable in platelets of eight patients and GP IIb was identified in five. Our findings suggest that residual quantities of GP IIb and GP IIIa are present in most patients with thrombasthenia and therefore that major deletions in the gene or genes encoding these proteins are uncommon.

scholarly journals Residual amounts of glycoproteins IIb and IIIa may be present in the platelets of most patients with Glanzmann's thrombasthenia

Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 1021-1024 ◽  
Author(s):  
AT Nurden ◽  
D Didry ◽  
N Kieffer ◽  
RP McEver
Keyword(s):  
Bleeding Disorder ◽  
Platelet Membrane ◽  
Type I ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Polyclonal Rabbit ◽  
Glanzmann's Thrombasthenia ◽  
Genes Encoding ◽  
Or Genes

Glanzmann's thrombasthenia is an inherited bleeding disorder characterized by abnormalities of platelet membrane glycoproteins (GP) IIb and IIIa. Most patients, usually designated as type I, have been reported to have undetectable levels of GP IIb and GP IIIa with the assay used. We have used polyclonal rabbit antibodies against GP IIb and GP IIIa in a sensitive immunoblot procedure capable of revealing trace amounts of these glycoproteins. Platelets from nine thrombasthenic patients, including seven with type I disease, were studied. GP IIIa, although decreased, was clearly detectable in platelets of eight patients and GP IIb was identified in five. Our findings suggest that residual quantities of GP IIb and GP IIIa are present in most patients with thrombasthenia and therefore that major deletions in the gene or genes encoding these proteins are uncommon.

Crossed Immunoelectrophoresis In The Identification Of Platelet Membrane Glycoproteins And Complexes

1981 ◽  
Author(s):  
S Karpatkin ◽  
S Shulman ◽  
L Howard ◽  
S Sadanandan
Keyword(s):  
Concanavalin A ◽  
Surface Antigens ◽  
Platelet Membrane ◽  
Surface Proteins ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Crossed Immunoelectrophoresis ◽  
Platelet Membranes ◽  
Glanzmann's Thrombasthenia ◽  
Major Antigen

Human platelet membranes were solubilized in 1% Triton X-100 and subjected to crossed immunoelectrophoresis, employing a rabbit anti-piatelet membrane antibody. Ten different antigens were observed fairly consistently; one could be identified as albumin, the other as fibrinogen. Surface antigens were determined by antibody adsorbtion experiments, and cell surface labeling with 125I-lactoperoxidase. Four surface antigens reacted with concanavalin A, when this was employed as an intermediate spacer gel. A major surface antigen, 10, was present on all preparations and was inversely related to antigens 13 and 18, which moved more cathodally. Membranes from preparations with full 10 antigen peaks had absent or diminished 13 and 18 antigen peaks, whereas preparations with absent to incomplete cathodal curves had increased 13 and 18 antigen peaks. Digestion of intact washed platelets with α chymotrypsin resulted in a decrease in the 10 antigen peak and an increase in 13 and 18, suggesting a structural relationship. Extraction of platelet membranes in EDTA or EGTA resulted in the disappearance of 10 and appearance of 13 and 18 (which react with concanavalin A) and 15 and 16 (which do not). Splitting of the major antigen into 13, 18, 15 and 16 could be prevented by addition of excess Ca++ relative to EGTA (but not by excess Mg++). Similar results were obtained in the absence of chelating agents following dialysis at 60-200 hrs against ‘Ca++-free’ buffer. Five patients with Glanzmann’s thrombasthenia have been studied. All k components of the major membrane antigen are missing. We conclude that the major antigen, 10, is composed of 2 glycoproteins, 13 and 18, and 2 other surface proteins, 15 and 16, which are held together by Ca++. It is conceivable that patients with Glanzmann’s thrombasthenia are lacking a membrane receptor for Ca++ or the platelet membrane (glyco)protein which anchors these A components.

FIBRINOGEN SYNTHESIS BUT DEFECTIVE STORAGE IN THE PLATELETS OF A PATIENT WITH GLANZMANN’S THROMBASTHENIA

1987 ◽  
Author(s):  
F Belloc ◽  
P Hourdille ◽  
M Boisseau ◽  
A T Nurden
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Type I ◽  
Membrane Glycoproteins ◽  
Chase Period ◽  
Glanzmann’S Thrombasthenia ◽  
Multiple Protein ◽  
Severe Deficiency ◽  
Glanzmann's Thrombasthenia ◽  
Sds Page ◽  
History Of

Patient A.M. has a lifelong history of bleeding episodes and platelet function defects typical of type I Glanzmann's thrombasthenia. Analysis of platelet membrane glycoproteins (GP) by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) or by studying the binding of monoclonal antibodies to intact platelets, confirmed the presence of only trace amounts of GP lib and GP Ilia. SDS-PAGE also revealed a severe deficiency of the alpha-granule pool of platelet fibrinogen although an immunoblot performed using a monospecific rabbit anti-fibrinogen antibody showed the presence of residual amounts of fibrinogen. This was estimated to be approximately 10 % of the normal range by an ELISA procedure. Incubation of washed platelets from A.M. with (35S) methionine for 3 h at 37°C resulted in the incorporation of radioactivity into multiple protein bands as revealed by SDS-PAGE followed by fluorography. Immunoprecipitation experiments with affinity purified anti-fibrinogen IgG bound to ultrogel confirmed the synthesis of fibrinogen. The amounts of radioactivity obtained were similar to those immunoprecipitated from control platelet extracts under the same conditions. However, unlike for control platelets, the neosynthesized fibrinogen in A.M. platelets was no longer detected after a 18 h cold chase. In contrast, neosynthesized thrombospondin of the patient was normally preserved during the same chase period. When the fate of the neosynthesized fibrinogen in A.M. platelets was studied it was found to be lost at a faster rate than in normal platelets. Immunoblotting experiments confirmed that cytoplasmic proteases may degrade fibrinogen when exposed to the protein. Our results suggest that the fibrinogen deficiency in the platelets of patients with type I thrombasthenia may be related to a storage abnormality in megakaryocytes or platelets and not from a synthesis defect.

Platelet Membrane Glycoproteins and their Possible Relationship to the ADP Mechanism of Platelet Aggregation

1975 ◽  
Author(s):  
D. R. Phillips ◽  
C. S. P. Jenkins ◽  
D. Meyer ◽  
M.-J. Larrieu ◽  
E. F. Luscher
Keyword(s):  
Platelet Aggregation ◽  
Surface Structure ◽  
Marked Reduction ◽  
Membrane Surface ◽  
Platelet Membrane ◽  
Membrane Glycoproteins ◽  
Altered Expression ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Induced Aggregation

Platelets isolated from patients with Glanzmann’s Thrombasthenia release in the presence of thrombin and other stimuli but fail to respond to ADP. Since the iutia.l interaction, between the platelet and ADP is at the membrane surface, it would appear that this surface lacks the necessary receptor for ADP. The surface structure of normal and thrombasthenia platelets was compared using the lactoperoxidase iodination technique. Iodination of normal platelets results in the labelling of four glycoproteins, I, IIa IIb and III, with relative ratios of 1 : 1 : 1 : 3 plus other non-characterised polypeptides. Thrombasthenic platelets similarly treated revealed a drastically altered expression of the glycoproteins on the membrane. The relative ratios (1.5: 1:0.4:0.5) revealed the decrease of glycoprotein IIb and the marked reduction of glycoprotein III. Arguments and data will be presented which point to the possibility that glycoprotein IIb is involved in ADP-induced aggregation.

scholarly journals Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 173-179
Author(s):  
LK Jennings ◽  
RA Ashmun ◽  
WC Wang ◽  
ME Dockter
Keyword(s):  
Flow Cytometry ◽  
Whole Blood ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Platelet Membrane ◽  
Parameter Analysis ◽  
Light Scatter ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia

Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet- rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the “platelet” light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins.

scholarly journals Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 173-179 ◽  
Author(s):  
LK Jennings ◽  
RA Ashmun ◽  
WC Wang ◽  
ME Dockter
Keyword(s):  
Flow Cytometry ◽  
Whole Blood ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Platelet Membrane ◽  
Parameter Analysis ◽  
Light Scatter ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia

Abstract Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet- rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the “platelet” light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins.

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