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

摘要: Matrix metalloproteinase (MMP)-8 and -9 released by degranulating polymorphonuclear cells (PMNs) promote pericellular proteolysis binding to PMN surfaces in a catalytically active tissue inhibitor of metalloproteinases (TIMP)-resistant forms. The receptor(s) which MMP-8 MMP-9 bind(s) is not known. Competitive experiments showed that Mmp-8 Mmp-9 share sites on murine surfaces. A novel form TIMP-1 (an soluble MMPs) rapidly expressed when human PMNs are activated. Membrane-bound the receptor for pro- as shown following: 1) strikingly colocalized with activated extracellular traps; 2) minimal immunoreactive or detected surface Timp-1-/- PMNs; 3) exogenous Timp-1 (but Timp-2) reconstitutes pro-Mmp-8 pro-Mmp-9 PMNs. Unlike full-length pro-Mmp-9, mutant pro-Mmp proteins lacking COOH-terminal hemopexin domain fail bind Mmp-8-/-x Mmp-9-/- Soluble inhibits Thus, domains required their membrane-bound Exposing nonhuman primates cigarette smoke upregulates expression peripheral blood By anchoring surfaces, plays counterintuitive role promoting occurring chronic obstructive pulmonary disease other diseases.