Natural human monocyte gelatinase and its inhibitor.
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 cross-reacted in immunoprecipitation 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.
Opdenakker
G
G
Rega Institute for Medical Research, University of Leuven, Belgium.
Masure
S
S
Proost
P
P
Billiau
A
A
van Damme
J
J
D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003429:Cross Reactions; D018093:Gelatinases; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000201:enzymology*; D010434:Pepsin A / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D011233:Precipitin Tests; D016415:Sequence Alignment; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D010434:Pepsin A; D018093:Gelatinases; D003012:Microbial Collagenase