Abstract

The formation of active matrix metalloprotease-2 (MMP-2) requires the proteolytic processing of proMMP-2, a process that can occur through the formation of a ternary complex between proMMP-2, the tissue inhibitor of metalloprotease-2 and membrane type 1-MMP. However, other activation mechanisms have been suggested, and in this study we investigated whether mast cells (MCs) may play a role in the activation of proMMP-2. Murine peritoneal cells, a mixture of macrophages, lymphocytes and MCs, were cultured ex vivo. Addition of proMMP-2 to resting peritoneal cell cultures resulted in only slow conversion of proMMP-2 into the active enzyme. However, when MC degranulation was provoked using a calcium ionophore, proMMP-2 processing was markedly enhanced. When the peritoneal cell populations were depleted in MCs, proMMP-2 processing was abrogated, but was reconstituted when purified MCs were added to the depleted cultures. ProMMP-2 processing was sensitive to serine protease inhibitors, but not to inhibitors of other classes of proteases. Furthermore, proMMP-2 processing was completely abrogated in cells lacking serglycin, a proteoglycan that has previously been shown to mediate storage of a variety of MC serine proteases. Taken together, these results suggest a novel mode of proMMP-2 activation mediated by serglycin-dependent MC serine proteases

Published in

Biological Chemistry
2006, Volume: 387, number: 10-11, pages: 1513-1519
Publisher: WALTER DE GRUYTER & CO

SLU Authors

• Pejler, Gunnar

  • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
    

• Åbrink, Magnus

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Veterinary Science
Animal and Dairy Science


Publication identifier

DOI: https://doi.org/10.1515/BC.2006.189

Permanent link to this page (URI)

https://res.slu.se/id/publ/10685