Tissue Inhibitor of Metalloproteinase-1 Promotes Polymorphonuclear Neutrophil (PMN) Pericellular Proteolysis by Anchoring Matrix Metalloproteinase-8 and -9 to PMN Surfaces.

ABSTRACT: Matrix metalloproteinase (MMP)-8 and -9 released by degranulating polymorphonuclear cells (PMNs) promote pericellular proteolysis by binding to PMN surfaces in a catalytically active tissue inhibitor of metalloproteinases (TIMP)-resistant forms. The PMN receptor(s) to which MMP-8 and MMP-9 bind(s) is not known. Competitive binding experiments showed that Mmp-8 and Mmp-9 share binding sites on murine PMN surfaces. A novel form of TIMP-1 (an inhibitor of soluble MMPs) is rapidly expressed on PMN surfaces when human PMNs are activated. Membrane-bound TIMP-1 is the PMN receptor for pro- and active MMP-8 and -9 as shown by the following: 1) TIMP-1 is strikingly colocalized with MMP-8 and -9 on activated human PMN surfaces and in PMN extracellular traps; 2) minimal immunoreactive and active Mmp-

SUBMITTER: Wang X 

PROVIDER: S-EPMC7347292 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature