Natural human monocyte gelatinase and its inhibitor

Abstract

Gelatinases produced by stimulated peripheral blood monocytes were detected by substrate zymography and were compared with those derived from tumor cells. Stimulated monocytes were found to produce an 85 kDa gelatinase which co-migrated upon electrophoretic separation and crossreacted in immunoprecipitat.ion experiments with a phorbol ester inducible metalloprotease from human tumor cells. The intact natural gelatinase (85 kDa), a high molecular weight and complexed gelatinase as well as a proteolytic fragment (25 kDa) were purified by substrate-and antibody affinity chromatography techniques. Aminoterminal sequence analysis showed that natural monocyte gelatinase occurs as a truncated form of tumor cell gelatinase/type IV collagenase. Furthermore, peripheral blood monocytes were found to also produce a tissue inhibitor of metalloproteases (TIMP). TIMP was co-purified with gelatinase on gelatin sepharose and identified by microsequencing. The balanced and regulated production of gelatinase and TIMP might be important in monocyte migration and tissue remodeling.

Matrix Metalloproteinase 9 (MMP-9)-dependent Processing of βig-h3 Protein Regulates Cell Migration, Invasion, and Adhesion

“…MMP-9 is mainly observed in neutrophils and macrophages in humans (45)(46)(47). Macrophages enhance tumor progression and metastasis (51).…”

Autocrine regulation of matrix metalloproteinase-9 gene expression and secretion by tumor necrosis factor-α (TNF-α) in NB4 leukemic cells: specific involvement of TNF receptor type 1

“…23 Monocytes, on the other hand, also release MMP-9 after stimulation with TPA but are not able to store the enzyme. 24 Interestingly, MMP-9 release is also observed in leukemia cell lines as well as in ex vivo cells from leukemia patients. 25,26 Recently, we described constitutive and stimulated MMP-9 secretion to be regulated by autocrine stimulation with TNF-␣ in HL-60 (FAB-M2) leukemic cells.…”

Production and Characterization of Recombinant Active Mouse Gelatinase B from Eukaryotic Cells and in vivo Effects after Intravenous Administration

“…Gelatinase B (92-kDa gelatinase) is the most complex MMP described so far and is secreted in a regulated manner by white blood cells (monocytes/macrophages, neutrophils, T-lymphocytes) and by many tumor cell lines (Wilhelm et al, 1989, Masure et al, 1990, 1991Opdenakker et al, 1991 a;Van Ranst et al, 1991 ;Montgomery et al, 1993). In vivo, it has been documented to be physiologically involved in bone resorption (Reponen et al, 1994;Tezuka et al, 1994;Okada et al, 1995) and in embryonal (cytotrophoblast) implantation (Librach et al, 1991).…”