Kupffer cell-derived 95-kd type iv collagenase/gelatinase b: characterization and expression in cultured cells

doi:10.1016/0270-9139(95)90385-2

Hepatology

Volume 22, Issue 1, July 1995, Pages 304-315

https://doi.org/10.1016/0270-9139(95)90385-2 Get rights and content

Abstract

Release of 92-kd type IV collagenase/gelatinase, also known as gelatinase B, by inflammatory and tumor cells is increasingly recognized and is believed to facilitate cellular migration across basement membranes. It has been implicated in the pathogenesis of many diseases, but little is known of its cellular origin(s) and function in liver. In this study we have demonstrated synthesis and release of gelatinase B by human and rat Kupffer cells in primary culture. Northern analysis of RNA extracted from Kupffer cells stimulated with phorbol ester demonstrated a 2.8 kb transcript for gelatinase B. Immunoblotting and zymography of serum-free Kupffer cell-conditioned media demonstrated extracellular release of immunoreactive enzyme and gelatinase activity, Mr 92,000 (95,000 from rat cells). The organomercurial 4-aminophenyl mercuric acetate (APMA) activated the enzyme in vitro, indicating secretion primarily as a proenzyme. Stimulation of Kupffer cells by phorbol ester markedly induced gelatinase B release, which was inhibited by cycloheximide. In contrast, cycloheximide had no effect on constitutive secretion in culture, suggesting that there is some intracellular storage. Kupffer cell-derived gelatinase B was also partially purified and characterized. After separation by gelatin sepharose and gel filtration chromatography, gelatin-degrading activities of 95, 88, 75, and 65 kd were detected, the three lower-molecular-weight species probably representing activated forms. Enzyme activity was inhibited by ethyl-enediaminetetra-acetic acid (EDTA), but not by serine-and thiol-protease inhibitors, and was restored by zinc. Activity was also inhibited by tissue inhibitor of metallo-proteinase-1 (TIMP-1) and α-2 macroglobulin. The partially purified enzyme rapidly degraded denatured collagens (gelatin) as well as native types III, IV, and V collagens, but had no activity against casein, types I and VI collagens.

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¹: P. J. Winwood was supported by the Wellcome Trust, London, United Kingdom (grant no. 031161/90/1.4G)

²: J. P. Iredale by the Medical Research Council of Great Britain (grant no. G84/2691).

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Kupffer cell-derived 95-kd type iv collagenase/gelatinase b: characterization and expression in cultured cells

Abstract

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Trends in Genetics

Gastroenterology

J Hepatol

Anal Biochem

Anal Biochem

J Biol Chem

Anal Biochem

Anal Biochem

Anal Biochem

J Biol Chem

J Biol Chem

Biochem Biophys Res Commun

Gastroenterology

Gastroenterology

Gastroenterology

Characterization of gelatinase from pig polymorphonuclear leucocytes

Biochem J

Neutral metalloproteinases produced by human mononuclear phagocytes: enzyme profile, regulation, and expression during cellular development

J Clin Invest

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

J Clin Invest

Characteristics of a 95kDa matrix metallo-proteinase produced by mammary carcinoma cells

Biochemistry

Nomenclature and glossary of the matrix metalloproteinases

Matrix

Metalloproteinases and tissue damage

Br J Rheumatol

Matrix degradation in the liver

Semin Liver Dis

Migration of polymorphonuclear leukocytes through human amnion membrane: a scanning electron microscopic study

Biol Chem Hoppe Seyler

Human T lymphocytes synthesize the 92kDa type IV collagenase (gelatinase B)

J Cell Physiol

Molecular architecture of basement membranes

FASEB J

Expression of gelatinase/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion

Clin Exp Metastasis

Lipocytes from normal rat liver release a neutral metalloproteinase that degrades basement membrane (type IV) collagen

J Clin Invest