| First Author | Lundequist A | Year | 2006 |
| Journal | Biol Chem | Volume | 387 |
| Issue | 10-11 | Pages | 1513-9 |
| PubMed ID | 17081126 | Mgi Jnum | J:122887 |
| Mgi Id | MGI:3715689 | Doi | 10.1515/BC.2006.189 |
| Citation | Lundequist A, et al. (2006) Mast cell-dependent activation of pro matrix metalloprotease 2: A role for serglycin proteoglycan-dependent mast cell proteases. Biol Chem 387(10-11):1513-9 |
| abstractText | 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. |
