Thromb Haemost 1995; 73(04): 702-705
DOI: 10.1055/s-0038-1653844
Original Articles
Platelets
Schattauer GmbH Stuttgart

Transformation of Cellular Factor XIII into an Active Zymogen Transglutaminase in Thrombin-Stimulated Platelets

László Muszbek
The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
,
Gizella Haramura
The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
,
János Polgár
The Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary
› Author Affiliations
Further Information

Publication History

Received 13 October 1994

Accepted after revision 09 January 1995

Publication Date:
09 July 2018 (online)

Summary

The cellular form of blood coagulation factor XIII (FXIII) is present in platelets, monocytes and macrophages. During long-term stimulation of platelets by thrombin cellular FXIII becomes activated and crosslinks proteins, however, the mechanism of its activation has not been elucidated. It was shown that, contrary to plasma FXIII, the intracellular activation of platelet FXIII does not involve proteolysis. FXIII remained intact in thrombin-activated platelets, i.e., the activation peptide was not removed from the molecule. Part of the zymogen FXIII molecules, however, assumed an active configuration as was demonstrated both by the measurement of transglutaminase activity and by active-site-SH titration. These findings clearly indicate that during platelet activation, when intracellular Ca2+ concentration is raised, a slow non-proteolytic transformation of FXIII zymogen into an active transglutaminase occurs.

 
  • References

  • 1 Muszbek L, Laki K. Interaction of thrombin with proteins other than fibrinogen (thrombin susceptible bonds). In: The Thrombin. Machovich R. (ed) CRC Press; Boca Raton: 1984. pp 83-102
  • 2 McDonagh J. Structure and function of factor XIII. In: Hemostasis and Thrombosis. 2 nd edition Colman RW, Hirsh J, Marder WJ, Salzman EW. eds Lippincott; Philadelphia PA: 1987. pp 289-300
  • 3 Board PG, Losowsky MS, Miloszewski KJ A. Factor XIII: Inherited and acquired deficiency. Blood Reviews 1993; 7: 229-242
  • 4 Buluk K. An unknown function of blood platelets. Pol Tyg Lek 1955; 10: 191
  • 5 Lüscher EF. Ein fibrinstabilisierender Factor aus Thrombozyten. Schweiz Med Wochenschr 1957; 87: 1220-1221
  • 6 Muszbek L, Ádány R, Szegedi G, Polgar J, Kávai M. Faxtor XIII of blood coagulation in human monocytes. Thromb Res 1985; 37: 401-410
  • 7 Ádány R, Belkin A, Vasilevskaya T, Muszbek L. Identification of blood coagulation Factor XIII in human peritoneal macrophages. Eur J Cell Biol 1985; 38: 171-173
  • 8 Henriksson P, Becker S, Lynch G, McDonagh JJ. Identification of intracellular factor XIII in human monocytes and macrophages. J Clin Invest 1985; 76: 528-534
  • 9 Kradin RL, Lynch GW, Kurnick JT, Erikson M, Colvin RB, McDonagh J. Factor XIIIA is synthesized and expressed on the surface of U937 cells and alveolar macrophages. Blood 1987; 69: 778-785
  • 10 Ádány R, Glukhova MA, Kabakov AY, Muszbek L. Characterization of human connective tissue cells containing factor XIII subunit a. J Clin Pathol 1988; 41: 49-56
  • 11 Muszbek L, Ádány R, Kávai M, Boda Z, Lopaciuk S. Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit a antigen and transglutaminase activity. Thromb Haemost 1988; 59: 231-235
  • 12 Muszbek L, Polgár J, Boda Z. Platelet Factor XIII becomes active without the release of activation peptide during platelet activation. Thromb Haemost 1993; 69: 282-285
  • 13 Ando Y, Imamura S, Yamagata Y, Kitahara A, Saji H, Murachi T, Kannagi R. Platelet factor XIII is activated by calpain. Biochem Biophys Res Commun 1987; 144: 484-490
  • 14 Credo RB, Curtis CG, Lorand L. Ca2+-related regulatory function of fibrinogen. Proc Natl Acad Sci USA 1978; 75: 4234-4237
  • 15 Lorand L. Activation of blood coagulation factor XIII. Ann NY Acad Sci 1986; 485: 144-158
  • 16 Polgár J, Hidasi V, Muszbek L. Nonproteolytic activtion of celllar protransglutaminase (placenta macrophage Factor XIII). Biochem J 1990; 267: 557-560
  • 17 Cooke RD, Holbrook JJ. Calcium and the assays of human plasma clotting Factor XIII. Biochem J 1974; 141: 71-78
  • 18 Bohn H, Schick HG. Isolierung und Charakterisierung eines fibrinstabilisierenden Faktors aus menschlichen Plazenten. Arzneim Forsch 1971; 21: 1432-1439
  • 19 McDonagh J, Waggoner WG, Hamilton EG, Hindenach B, McDonagh RP. Affinity chromatography of human plasma and platelet factor XIII on organomercurial agarose. Biochim Biophys Acta 1976; 446: 345-357
  • 20 Lorand L, Campbell-Wilkes LK, Cooperstein L. A filter paper assay for transamidating enzymes using radioactive amine substrates. Anal Biochem 1972; 50: 623-631
  • 21 Muszbek L, Polgár J, Fésüs L. Kinetic determination of blood coagulation Factor XIII in plasma. Clin Chem 1985; 31: 35-40
  • 22 Muszbek L, Laposata M. Glycoprotein Ib and glycoprotein IX in human platelets are acylated with palmitic acid through thioester linkages. J Biol Chem 1989; 264: 9716-9719
  • 23 Hársfalvi J, Fésüs L, Tarcsa E, Laczkó J, Loewy AG. The presence of a covalently cross-linked matrix in human platelets. Biochim Biophys Acta 1991; 1073: 268-274
  • 24 Curtis CG, Stenberg P, Chou C HJ, Gray A, Brown KL, Lorand L. Titration and subunit localization of active center cysteine in fibrinoligase (thrombin- activated fibrin stabilizing factor). Biochem Biophys Res Commun 1973; 52: 51-56
  • 25 Curtis CG, Brown KL, Credo RB, Domanik RA, Gray A, Stenberg P, Lorand L. Calcium-dependent unmasking of active center cysteine during activation of fibrin stabilizing factor. Biochemistry 1974; 13: 3774-80
  • 26 Cohen I, Glaser T, Veis A, Brunner-Lorand J. Ca2+dependent crosslinking process in human platelets. Biochim Biophys Acta 1981; 676: 137-147
  • 27 Cohen I, Young-Bandala L, Blankenberg TA, Sieffing GE, Brunner-Lorand J. Fibrinoligase-catalayzed cross-linking of myosin from platelet and skeletal muscle. Arch Biochem Biophys 1979; 192: 100-111
  • 28 Cohen I, Blankenberg TA, Borden K, Kahn DR, Veis A. Factor XIIIa- catalyzed cross-linking of platelet and muscle actin. Biochim Biophys Acta 1980; 628: 365-375
  • 29 Asijee GM, Muszbek L, Kappelmayer J, Polgár J, Horvath A, Sturk G. Platelet vinculin: a substrate of activated Factor XIII. Biochim Biophys Acta 1988; 954: 303-308