Characterization and Origin of Fibrinogen in Blood Platelets

Harold L. James; Pankaj Ganguly; Carl W. Jackson

doi:10.1055/s-0038-1651912

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1977; 38(04): 0939-0954
DOI: 10.1055/s-0038-1651912

Original Article

Schattauer GmbH

Characterization and Origin of Fibrinogen in Blood Platelets

A Review with Recent Data

Authors

Harold L. James^*

¹Laboratory of Hematology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38101, U.S.A.
Pankaj Ganguly

¹Laboratory of Hematology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38101, U.S.A.
Carl W. Jackson

¹Laboratory of Hematology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38101, U.S.A.

Abstract

Summary

The discovery of thrombin-clottable protein in platelet homogenates initiated studies on the location, properties, and origin of such material, the ultimate aim of which has been to define its physiologic role. It was established that fibrinogen is present both on the platelet membrane as well as in the cytoplasmic α-granules. The membrane-bound material is apparently fibrinogen adsorbed from plasma, while the intracellular fibrinogen appears to have unique biochemical and functional properties. Differences in properties observed between platelet fibrinogen and plasma fibrinogen are not due to in vitro modifications during handling. Whether the intracellular fibrinogen is synthesized in the platelet (or megakaryocyte) or whether it is derived through uptake and limited modification of plasma fibrinogen in vivo has remained an open question. Thus, to investigate the aspect of origin of platelet fibrinogen, radioactively-labelled fibrinogen was injected into rats, blood was collected at time intervals and the radioactivity in the subcellular fractions of platelets was examined. A part of the injected fibrinogen became associated with the platelets, but very little was found in the granule fraction. Previous findings on human platelet fibrinogen, together with the present data obtained using rats, suggest that platelet fibrinogen may not be derived from plasma fibrinogen in vivo. It thus is apparent that the intracellular fibrinogen is synthesized by a unique genetic mechanism. Molecular properties of fibrinogen derived from rat platelet granules were shown analogous to the properties of fibrinogen from human platelet granules. Fibrinogen of intracellular origin is less stable than its plasma counterpart. The results obtained by others in which identity of platelet and plasma fibrinogens was reported may be explained on the basis of recovery of only the fibrinogen component bound to the platelet membrane, which is adsorbed plasma fibrinogen. It is suggested that the term platelet fibrinogen may be used to denote that present in the α-granules, with the membrane-bound component being referred to as platelet-associated fibrinogen.

Full Text

References

References
1 Bezkorovainy A, Rafelson Jr. M. E. 1964; Characterization of some proteins from normal human platelets. Journal of Laboratory and Clinical Medicine 64: 212.
2 Brecher G, Cronkite E. P. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365.
3 Castaldi P. A, Caen J. 1965; Platelet fibrinogen. Journal of Clinical Pathlogy 18: 579.
4 Cooper I. A, Firkin B. G. 1970; Amino acid transport in human platelets and subsequent incorporation into platelets. Thrombosis et Diathesis Haemorrhagica 23: 140.
5 Davey M. G, LÜscher E. F. 1967. Platelet proteins. In: Niewiarowski S, Kowalski E. (eds.) Biochemistry of Blood Platelets. Academic Press; London/New York: 9.
6 Davey M. G, Lüscher E. F. 1968; Release reactions of human platelets induced by thrombin and other agents. Biochimica et biophysica acta 165: 490.
7 Day H. J, Solum N. O. 1973; Fibrinogen associated with subcellular platelet particles. Scandinavian Journal of Haematology 10: 136.
8 Doolittle R. F, Takagi T, Cottrell B. A. 1974; Platelet and plasma fibrinogens are identical gene products. Science 185: 368.
9 Droller M. J. 1973; Ultrastructural visualization of the thrombin-induced platelet release reaction. Scandinavian Journal of Haematology 11: 35.
10 Edgington T. S, Plow E. F. 1974; Immunochemical differences between plasma fibrinogen and platelet fibrinogen. Federation Proceedings 33: 218 (Abstr. No. 84).
11 Ganguly P. 1969; Effect of proteolytic activity on the isolation and stability of platelet proteins. Clinica Chimica Acta 25: 371.
12 Ganguly P. 1972; Isolation and some properties of fibrinogen from human blood platelets. Journal of Biological Chemistry 247: 1809.
13 Gokcen M, Yunis E. 1963; Fibrinogen as a part of platelet structure. Nature 200: 590.
14 Grette K. 1962; Studies on the mechanism of thrombin-catalyzed hemostatic reactions in blood platelets. Acta Physiologica Scandinavica 56 (Suppl. 195) 1.
15 Holme R, Sixma J. J, Mürer E. H, Hovig T. 1973; Demonstration of platelet fibrinogen secretion via the surface connecting system. Thrombosis Research 3: 347.
16 James H. L, Bradford H. R, Ganguly P. 1974; Quantitation of human platelet fibrinogen. Circulation 50: III-284 (Abstr. No. 1084).
17 James H. L, Bradford H. R, Ganguly P. 1975; Platelet fibrinogen. Identity and initial observations on the mode of its degradation by plasmin. Biochimica et biophysica acta 386: 209.
18 James H. L, Ganguly P. 1973; Studies on platelet proteins IX. The identity of fibrinogen. Biochimica et biophysica acta 328: 448.
19 James H. L, Ganguly P. 1975; Identity of human platelet fibrinogen. Biochemical and Biophysical Research Communications 63: 659.
20 Johnson S. A, Monto R. W, Caldwell M. J. 1958; Relationship of platelet factor 1 and platelet fibrinogen to plasma. Journal of Applied Physiology 13: 406.
21 Johnson S. A, Schneider C. L. 1953; The existence of antifibrinolysis activity in platelets. Science 117: 229.
22 Johnsson H. 1975; On platelet fibrinogen in plasma defibrinogenated dogs and in uremic patients before and after hemodialysis. Thrombosis Research 7: 161.
23 Joist J. H, Niewiarowski S. 1973; Retention of platelet fibrin stabilizing factor during the platelet release reaction and clot retraction. Thrombosis et Diathesis Haemorrhagica 29: 679.
24 Kazal L. A, Amsel S, Miller O. D, Tocantins L. M. 1963; The preparation and some properties of fibrinogen precipitated from human plasma by glycine. Proceedings of the Society for Experimental Biology and Medicine 113: 989.
25 Keenan J. P. 1972; Platelet fibrinogen. I Quantitation using fibrinogen sensitized tanned red cells. Medical Laboratory Technology 29: 71.
26 Keenan J. P, Solum N. O. 1972; Quantitative studies on the release of platelet fibrinogen by thrombin. British Journal of Haematology 23: 461.
27 Kuhnke E. 1962; Ein neuer Fibrillentyp in thrombozytenhaltigen Fibringerinnseln. Naturwissenschaften 49: 60.
28 Lang C. A. 1958; Simple micro-determination of Kjeldahl nitrogen in biological materials. Analytical Chemistry 30: 1692.
29 Levin R. H, Freireich E. J. 1964; Effect of storage up to 48 hours on response to transfusion of platelet rich plasma. Transfusion 4: 251.
30 Łopaciuk S, Lovette K. M, McDonaugh R. P, Chuang H. Y. K, McDonaugh J. M. 1975; Subcellular distribution of fibrinogen and factor XIII in human blood platelets. Federation Proceedings 34: 344 (Abstr. No. 708).
31 Łopaciuk S, Solum N. O. 1969; Bovine platelet proteins I. Soluble proteins studied by Immunoelectrophoresis and polyacrylamide disc electrophoresis. Thrombosis et Diathesis Haemorrhagica 21: 409.
32 Lüscher E. F. 1953; Fibrinretraktion und thrombocytenproteine. Helvetica Physiologica et Pharmacologica Acta 11: C64.
33 Lüscher E. F. 1959; Thrombocytenfaktoren. Ergebnisse der Physiologie 50: 1.
34 Marcus A. J, Zucker M. B. 1965. The Physiology of Blood Platelets. Grune and Stratton; New York, London.:
35 Marcus A. J, Zucker-Franklin D, Saher L. B, Ullman H. L. 1966; Studies on human platelet granules and membranes. Journal of Clinical Investigation 45: 14.
36 Marder V. J, Shulman N. R, Carroll W. R. 1969; High molecular weight derivatives of human fibrinogen produced by plasmin. I. Physicochemical and immunological characterization. Journal of Biological Chemistry 244: 2111.
37 Mcfarlane A. S. 1963; In vivo behavior of I¹³¹-fibrinogen. Journal of Clinical Investigation 42: 346.
38 Mui P. T. K, Ganguly P. 1976; Covalent cross-linking of actin and fibrin by fibrin-stabilizing factor. Circulation 53/54: II-201 (Abstr. No. 788).
39 Nachman R. L. 1965; Immunologic studies of platelet protein. Blood 25: 703.
40 Nachman R. L, Marcus A. J, Zucker-Franklin D. 1964; Subcellular localization of platelet fibrinogen. Blood 24: 853.
41 Nachman R. L, Marcus A. J, Zucker-Franklin D. 1967; Immunologic studies of proteins associated with subcellular fractions of normal human platelets. Journal of Laboratory and Clinical Medicine 69: 651.
42 Nadelhaft I, Lamy F. 1972; Fibrinogen turnover in rats as a function of age. Journal of Laboratory and Clinical Medicine 79: 724.
43 Niewiarowski S. 1977; Proteins secreted by the platelet. Thrombosis and Haemostasis 38: 924.
44 Niewiarowski S, Senyi A. F, Gillies P. 1973; Plasmin-induced platelet aggregation and platelet release reaction. Journal of Clinical Investigation 52: 1647.
45 Plow E. F, Edgington T. S. 1975; Unique immunochemical features and intracellular stability of platelet fibrinogen. Thrombosis Research 7: 729.
46 Rosier O, Wegrzynowicz A, Sawicki A, Kopec M. 1970; Fibrinogensynthese in Blutplättchen. Folia Haematologica 92: 553.
47 Roskam J. 1923; Contribution a l’étude de la physiologie normale et pathologique du globulin. Archives Internationales de Physiologie 20: 241.
48 Salmon J, Bounameaux Y. 1956; Recherches sur l’antigénicité des plaquettes et du fibrinogène bovins. Comptes Rendus des Seances de la Societe de Biologie 150: 2278.
49 Salmon J, Bounameaux Y. 1958; Etude des antigènes plaquettaires et, en particulier, du fibrinogène. Thrombosis et Diathesis Haemorrhagica 2: 93.
50 Salmon J, Verstraete M, Bounameaux Y. 1957; Fibrinogène plaquettaire et afibrinogénémie. Archives Internationales de Physiologie et de Biochimie 65: 632.
51 Scheidegger J. J. 1955; Une micro-method de l’immuno-electrophorese. International Archives of Allergy 7: 103.
52 Schmid H. J, Jackson D. P, Conley C. L. 1962; Mechanism of action of thrombin on platelets. Journal of Clinical Investigation 41: 543.
53 Seligmann M, Goudeman B, Janin A, Bernard J, Grabar P. 1957; Études immuno-chimiques sur la présence de fibrinogène dans des extraits de plaquettes humaines lavées et dans certains extraits leucocytaires. Revue d’Hematologie 12: 302.
54 Sokal G. 1962; Étude morphologique des plaquettes sanguines et de la métamorphose visqueuse au moyen d’antisérums fluorescents antifibrinogène et antiplaquettes. Acta Haematologica 28: 313.
55 Solum N. O, Łopaciuk S. 1969; a Bovine platelet proteins II. Purification of platelet fibrinogen. Thrombosis et Diathesis Haemorrhagica 21: 419.
56 Solum N. O, Łopaciuk S. 1969; b Bovine platelet proteins III. Some properties of platelet fibrinogen. Thrombosis et Diathesis Haemorrhagica 21: 428.
57 Tangen O, McKinnon E. L, Berman H. J. 1973; On the fine structure and aggregation requirements of gel filtered platelets (GFP). Scandinavian Journal of Haematology 10: 96.
58 Tollefsen D. M, Majerus P. W. 1975; Inhibition of human platelet aggregation by monovalent antifibrinogen antibody fragments. Journal of Clinical Investigation 55: 1259.
59 Ware A. G, Fahey J. L, Seegers W. H. 1948; Platelet extracts, fibrin formation and interaction of purified prothrombin and thromboplastin. American Journal of Physiology 154: 140.
60 Warshaw A. L, Laster L, Shulmán N. R. 1967; Protein synthesis by human platelets. Journal of Biological Chemistry 242: 2094.
61 Weber K, Osborn M. 1969; The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. Journal of Biological Chemistry 224: 4406.
62 White J. G, Krivit W, Vernier R. L. 1965; The platelet-fibrin relationship in human blood clots: An ultrastructural study utilizing ferritin-conjugated anti-human fibrinogen antibody. Blood 25: 241.