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Thromb Haemost 2007; 98(02): 359-367
DOI: 10.1160/TH07-02-0098
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot

Zsuzsa Bagoly
1   University of Debrecen, Medical and Health Science Center, Clinical Research Center and Thrombosis and Haemostasis Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
,
Gizella Haramura
1   University of Debrecen, Medical and Health Science Center, Clinical Research Center and Thrombosis and Haemostasis Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
,
László Muszbek
1   University of Debrecen, Medical and Health Science Center, Clinical Research Center and Thrombosis and Haemostasis Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
› Author AffiliationsFinancial support: This work was supported by grants from the Hungarian National Research Fund (OTKA-NKTH NI 69238), from the Hungarian Academy of Sciences (MTA 11003, 2006TKI227), from the Hungarian Ministry of Health and Social Affairs (ETT 406/2006) and from the National Office of Research and Technology (NKTH-OTKA, RET-06/2004).
Further Information

Publication History

Received 08 February 2007

Accepted after revision 04 May 2007

Publication Date:
28 November 2017 (online)

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Summary

Activated clotting factors are down-regulated by two major mechanisms which involve protease inhibitors or proteolytic degradation. To date, no down-regulating mechanism for activated factor XIII (FXIIIa) has been demonstrated. As the hemostatic plug contains polymorphonuclear granulocytes (PMNs) rich in proteolytic enzymes, we tested if these proteases are released in fibrin clots, and become involved in the down-regulation of FXIIIa.The supernatant of stimulated granulocytes proteolytically degraded and inactivated FXIIIa. In the fibrin clot formed from fibrinogen solution elastase, cathepsin G and matrix metalloprotease-9 (MMP-9) were released from granulocytes without any external stimulus. PMN proteases released in fibrin clot exerted a fibrinolytic effect and almost completely de-graded both FXIII subunits.The elastase inhibitor, ONO 5046, partially inhibited the proteolytic degradation of FXIII in PMNsupplemented fibrin clots. Cathepsin G and MMP-9 inhibitors provided less protection; in these cases intermediate split products accumulated.The proteolytic degradation of FXIII by PMNs was also significant when the clot was made from whole plasma. The main plasma protease inhibitor, α1-antitrypsin, provided only partial protection. In the fibrin clot which contained α1-antitrypsin FXIIIa was degraded by PMN proteases significantly faster than cross-linked fibrin.The results suggest that the degradation of FXIII subunits by the concerted action of PMN proteases released within the clot represents a novel mechanism for the down-regulation of FXIIIa.

Keywords

Elastase - factor XIII - fibrinogen - fibrin - polymorphonuclear granulocytes
 

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