Progelatinase B Forms from Human Neutrophils. Complex Formation of Monomer/Lipocalin with TIMP-1

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Abstract
The three forms of neutrophil gelatinase B-monomer, homodimer and monomer/lipocalin complex-, were isolated from phorbolester stimulated neutrophil granulocytes by chromatography on gelatin-Sepharose and heparin-Ultrogel. On average, about 50% of the monomer/lipocalin complex was found to be complexed with TIMP-1. After activation with trypsin monomer, homodimer and monomer/lipocalin complex displayed a specific activity of about 2000 mU/mg towards the substrate N-(2,4)-dinitrophenyl-Pro-Gln-Gly-lle-Ala-Gly-Gln-D-Arg, whereas the monomer/lipocalin/TIMP-1 complex could be activated to a specific activity of only 200 mU/mg. The ternary monomer/lipocalin/TIMP-1 complex behaves like the progelatinase A-TIMP-2 complex and the progelatinase B-TIMP-1 complex in that it is an inhibitor for active metalloproteinases (MMPs) and, after activation, a gelatinase with a pronouncedly reduced activity. When the monomer/lipocalin/TIMP-1 complex inhibits an MMP, a quaternary complex monomer/lipocalin/TIMP-1/MMP is generated which after activation shows a sixfold higher proteolytic activity than the active ternary complex.