Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages.

Hibbs, Margaret S.; Hoidal, John R.; Kang, Andrew H.

doi:10.1172/jci113253

Cited by 219 publications

(97 citation statements)

References 40 publications

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“…Distribution of protein was shown to be similar to that of the mRNA (Figure 2b). As well as stromal distribution within spindle shaped cells, 92 kDa mRNA and protein was also identified in putative myoepithelial cells in some areas of ductal carcinoma in situ adjacent to the invasive carcinoma (Figure 2c and d (Hibbs et al, 1987;Welgus et al, 1990) and this activity is affected by, for example, treatment with LPS or concanavalin A. The tissue location of macrophages also affects the extent to which they express this enzyme, but the precise control mechanisms and mediators operating in vivo have not yet been elucidated.…”

Section: Localisation Of Type IV Collagenase Expressionmentioning

confidence: 91%

Activity of type IV collagenases in benign and malignant breast disease

Davies¹,

Miles²,

Happerfield³

et al. 1993

Br J Cancer

308

155

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Using zymography and computer assisted image analysis, we have measured the levels of type IV collagenases in biopsies from normal breast, and benign and malignant breast disease. The 92 kDa form was present in three of 11 cases of normal/benign disease, three of nine grade I tumours, four of 12 grade II tumours, but 11 of 11 grade III tumours. Mean levels were higher in grade III tumours (P < 0.0001). When the levels of 72 kDa collagenase and its active 62 kDa form were considered together, there was no difference between the benign and malignant cases (P = 0.55), but the amount of active enzyme, considered as a proportion of the 62 + 72 kDa forms, was significantly higher in malignant disease (P = 0.003). There was also a trend towards a higher proportion of active enzyme with increasing tumour grade (P < 0.0001). In situ hybridisation and immunohistochemistry studies showed that that mRNA and protein for the 92 kDa enzyme was primarily found in the tumour stroma. mRNA for the 72 kDa enzyme was also found in stromal areas. This study demonstrates a clear relationship between production of Type IV collagenases and malignant breast disease. Inhibitors of these enzymes may be of value in preventing metastatic disease. Images Figure 1 Figure 2

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Section: Localisation Of Type IV Collagenase Expressionmentioning

confidence: 91%

Activity of type IV collagenases in benign and malignant breast disease

Davies¹,

Miles²,

Happerfield³

et al. 1993

Br J Cancer

308

155

View full text Add to dashboard Cite

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“…Ethidium bromide staining of 28S ribosomal RNA was used to document equal loading of RNA in each lane. tified in polymorphonuclear leukocytes and macrophages (33,34), is produced by a small number of cell types. However, its expression can be readily regulated by a number of agents, including growth factors, hormones, cytokines, and extracellular matrix molecules (35), which explains why MMP9 is often associated with inflammation, tissue injury and tumor invasion.…”

Section: Fig 5 Northern Blot Analysis Of Large-t Egf (15 Ng/ml) Amentioning

confidence: 99%

Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor

Piedagnel

Murphy

Ronco

et al. 1999

Journal of Biological Chemistry

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We analyzed the expression and regulation of matrix metalloproteinase 2 (MMP2) and MMP9 gelatinases in a rabbit kidney collecting duct principal cell line (RC.SVtsA58) (Prié , D., Ronco, P. M., Baudouin, B., Gé niteauLegendre, M., Antoine, M., Piedagnel, R., Estrade, S., Lelongt, B., Verroust, P. J., Cassingé na, R., and Vandewalle, A. (1991) J. Cell Biol. 113, 951-962) infected with the temperature-sensitive (ts) SV40 strain tsA58. At the permissive temperature (33°C), cells produced only MMP2. Shifting cells to a nonpermissive temperature (39.5°C) induced a marked increase in total gelatinolytic activity due to an increase of MMP2 and an induction of MMP9 synthesis. This effect was attributed to large-T inactivation at 39.5°C because it was abolished by re-infecting the cells with wild-type SV40 strain LP. Run-on experiments showed that negative regulation of MMP2 and MMP9 by large-T was transcriptional and posttranscriptional, respectively. MMP2 and MMP9 were also produced by primary cultures of collecting duct cells. In rabbit kidney, both MMP2 and MMP9 were almost exclusively expressed in collecting duct cells, where an unexpected apical localization was observed. Arginine vasopressin and epidermal growth factor, which exert opposite hydroosmotic effects in the collecting duct, also exhibited contrasted effects on MMP9 synthesis. Epidermal growth factor increased but arginine vasopressin suppressed MMP9 at a posttranscriptional level, whereas MMP2 was not affected. These results suggest a specific physiological role of MMP2 and MMP9 in principal cells of renal collecting duct.

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“…Macrophages secrete a metalloproteinase that digests gelatins and type-V collagen (Mainardi et al, 1984). These enzymes have now been shown by immunochemical criteria to be identical with the 92 kDa form of gelatinase/type-IV collagenase from various transformed cells (Hibbs et al, 1987;Murphy et al, 1989b;Wilhelm et al, 1989;Moll et al, 1990). According to the numerical distinction of the members of the MMP family, the 72 kDa and the 92 kDa zymogens are designated proMMP-2 and proMMP-9 (Nagase et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells

Morodomi

Osuga

Sasaguri

et al. 1992

Biochemical Journal

185

126

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603The precursor of matrix metalloproteinase 9 (proMMP-9), also known as '92 kDa progelatinase/type IV procollagenase', was purified from the conditioned medium of U937 monocytic leukaemia and HT1080 fibrosarcoma cell lines stimulated with phorbol 12-myristate 13-acetate. ProMMP-9 in these culture media is non-covalently complexed with the 29 kDa tissue inhibitor of metalloproteinases (TIMP), but free proMMP-9 was separated from the TIMP-proMMP-9 complex by chromatography on Green A Dyematrex gel. The final product was homogeneous on SDS/PAGE, with a molecular mass of 88 kDa without reduction and 92 kDa with reduction. Treatment of proMMP-9 with 4-aminophenylmercuric acetate converted the 88 kDa precursor into 80 kDa and 68 kDa forms. Gelatin-containing zymographic analysis showed zones of lysis associated with all three species. However, only the 68 kDa species was shown to be catalytically active by its ability to bind to a2-macroglobulin. In the presence of an equimolar amount of TIMP, only the 80 kDa species was generated by treatment with 4-aminophenylmercuric acetate, but no enzyme activity was detected. This indicates that TIMP binds to the 80 kDa intermediate and inhibits the generation of the active 68 kDa species. Eight endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, cathepsin G, neutrophil elastase and thermolysin) were tested for their ability to activate proMMP-9. Of them, trypsin was the most effective activator of proMMP-9. Only partial activation (10-30%) was observed with plasmin, cathepsin G and chymotrypsin. The active forms generated by trypsin were identified as 80 kDa, 74 kDa and 66 kDa by their abilities to bind to a2-macroglobulin. In the presence of an equimolar amount of TIMP, proMMP-9 was also converted into the same molecular-mass species by trypsin, but they were not proteolytically active. This suggests activated MMP-9 is inhibited by TIMP. Activated MMP-9 digested gelatin, type-V collagen, reduced carboxymethylated transferrin and, to a lesser extent, type-IV collagen and laminin A chain. The specific activity against gelatin was estimated to be 15000 units/mg (1 unit = 1 ,ug of gelatin degraded/min at 37°C) by titration with a2-macroglobulin. Comparative studies on digestion of gelatin and collagen types IV and V by MMP-9 and MMP-2 indicated that both enzymes degrade these substrates into similar fragments. However, the susceptibilities of laminin, fibronectin and reduced carboxymethylated transferrin to these two MMPs were sufficiently different to indicate differences in substrate specificities between these two closely related proteinases.

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Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages.

Cited by 219 publications

References 40 publications

Activity of type IV collagenases in benign and malignant breast disease

Activity of type IV collagenases in benign and malignant breast disease

Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor

Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells

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