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Regulation of extravascular coagulation and fibrinolysis by heparin-dependent mast cell chymase.
Swedish University of Agricultural Sciences, Department of Veterinary Medical Chemistry,.
Swedish University of Agricultural Sciences, Department of Veterinary Medical Chemistry,.
2001 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 15, no 14, 2763-5 p.Article in journal (Refereed) Published
Abstract [en]

We recently characterized a heparin-deficient mouse strain generated by targeting the gene for N-deacetylase/N-sulfotransferase-2 (NDST-2). The NDST-2-/- mice show severe defects in their organization of mast cell (MC) secretory granules, with an almost total absence of the various heparin-binding MC proteases. In the present report we have studied the consequences of heparin/MC protease deficiency for extravascular coagulation and fibrinolysis. Addition of prothrombin to peritoneal cells-a mixture of macrophages, lymphocytes, and MCs-resulted in formation of thrombin but the accumulation of thrombin occurred faster in the NDST-2-/-cells than in normal controls. Further, the generated thrombin was subsequently inactivated in the NDST-2+/+ cell cultures but not in the NDST-2-/- cells. Plasminogen was activated to plasmin at an apparently higher rate in peritoneal cells from NDST-2 null mice than in the normal controls. Similar to thrombin, the generated plasmin was inactivated by NDST-2+/+ but not by the NDST-2-/- cells. Subsequent experiments with normal cells showed that cell surface-associated MC chymase, in a strongly heparin-dependent manner, was responsible for both the thrombin-inactivating- and plasmin-inactivating activities. These results show that MC chymase-heparin complexes have the potential to regulate extravascular coagulation processes, as well as the plasminogen activator/plasmin system.

Place, publisher, year, edition, pages
2001. Vol. 15, no 14, 2763-5 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-160057DOI: 10.1096/fj.01-0486fjePubMedID: 11687508OAI: oai:DiVA.org:uu-160057DiVA: diva2:447891
Available from: 2011-10-13 Created: 2011-10-13 Last updated: 2015-07-01

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