Abstract
The topographic relationships of platelet membrane glycoprotein IIb and glycoprotein IIIa have been studied in stimulated and unstimulated human platelets using immunoelectron microscopy. An indirect approach with ferritin-conjugated goat anti-rabbit gamma-globulin was used to localize the rabbit antibody to glycoprotein IIIa. The second ultrastructural label was keyhole limpet hemocyanin conjugated directly to antibody to glycoprotein IIb. Using the double labels, it was demonstrated that glycoprotein IIb and glycoprotein IIIa were distributed randomly in the unstimulated platelet membrane. After platelet stimulation with thrombin, large clusters of glycoprotein IIb- glycoprotein IIIa complexes were formed. No complex formation between glycoprotein Ib and glycoprotein IIb was observed in control experiments. These observations suggest that thrombin stimulation initiates the specific glycoprotein IIb-glycoprotein IIIa macromolecular complex formation on the platelet surface, which may act as the active fibrinogen-binding site required for normal platelet aggregation.
Full Text
The Full Text of this article is available as a PDF (3.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ainsworth S. K., Karnovsky M. J. An ultrastructural staining method for enhancing the size and electron opacity of ferritin in thin sections. J Histochem Cytochem. 1972 Mar;20(3):225–229. doi: 10.1177/20.3.225. [DOI] [PubMed] [Google Scholar]
- Bennett J. S., Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest. 1979 Nov;64(5):1393–1401. doi: 10.1172/JCI109597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagen I., Nurden A., Bjerrum O. J., Solum N. O., Caen J. Immunochemical evidence for protein abnormalities in platelets from patients with Glanzmann's thrombasthenia and Bernard-Soulier syndrome. J Clin Invest. 1980 Mar;65(3):722–731. doi: 10.1172/JCI109719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karnovsky M. J., Unanue E. R., Leventhal M. Ligand-induced movement of lymphocyte membrane macromolecules. II. Mapping of surface moieties. J Exp Med. 1972 Oct 1;136(4):907–930. doi: 10.1084/jem.136.4.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leung L. L., Kinoshita T., Nachman R. L. Isolation, purification, and partial characterization of platelet membrane glycoproteins IIb and IIIa. J Biol Chem. 1981 Feb 25;256(4):1994–1997. [PubMed] [Google Scholar]
- Levy-Toledano S., Tobelem G., Legrand C., Bredoux R., Degos L., Nurden A., Caen J. P. Acquired IgG antibody occurring in a thrombasthenic patient: its effect on human platelet function. Blood. 1978 Jun;51(6):1065–1071. [PubMed] [Google Scholar]
- Marguerie G. A., Plow E. F., Edgington T. S. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem. 1979 Jun 25;254(12):5357–5363. [PubMed] [Google Scholar]
- McEver R. P., Baenziger N. L., Majerus P. W. Isolation and quantitation of the platelet membrane glycoprotein deficient in thrombasthenia using a monoclonal hybridoma antibody. J Clin Invest. 1980 Dec;66(6):1311–1318. doi: 10.1172/JCI109983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nachman R. L., Jaffe E. A., Weksler B. B. Immunoinhibition of ristocetin-induced platelet aggregation. J Clin Invest. 1977 Jan;59(1):143–148. doi: 10.1172/JCI108612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nurden A. T., Caen J. P. The different glycoprotein abnormalities in thrombasthenic and Bernard-Soulier platelets. Semin Hematol. 1979 Jul;16(3):234–250. [PubMed] [Google Scholar]
- Peerschke E. I., Zucker M. B. Fibrinogen receptor exposure and aggregation of human blood platelets produced by ADP and chilling. Blood. 1981 Apr;57(4):663–670. [PubMed] [Google Scholar]
- Peerschke E. I., Zucker M. B., Grant R. A., Egan J. J., Johnson M. M. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood. 1980 May;55(5):841–847. [PubMed] [Google Scholar]
- Plow E. F., Marguerie G. A. Participation of ADP in the binding of fibrinogen to thrombin-stimulated platelets. Blood. 1980 Sep;56(3):553–555. [PubMed] [Google Scholar]
- Polley M. J., Nachman R. The human complement system in thrombin-mediated platelet function. J Exp Med. 1978 Jun 1;147(6):1713–1726. doi: 10.1084/jem.147.6.1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TAWDE S. S., RAM J. S. Conjugation of antibody to ferritin by means of p,p'-difluoro-m, m'-dinitrodiphenylsulphone. Arch Biochem Biophys. 1962 May;97:429–430. doi: 10.1016/0003-9861(62)90102-9. [DOI] [PubMed] [Google Scholar]