Collagenase is a component of the specific granules of human neutrophil leucocytes

Murphy, Gillian; Reynolds, J J; Bretz, Ursula; Baggiolini, Marco

doi:10.1042/bj1620195

Cited by 161 publications

(78 citation statements)

References 22 publications

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“…The data in the present report indicate that undifferentiated U937 cells produce negligible amounts of collagenase, but differentiation induced by TPA results in a dramatic increase in collagenase production and the collagenase released by differentiated cells is immunologically and functionally identical to alveolar macrophage collagenase and thus distinct from the collagenolytic enzyme found in neutrophils. Macrophage and neutrophil collagenases are readily distinguished by their opposite selectivities against monomeric type I and III collagens (27), by their lack of cross-reactivity to monoclonal and polyclonal antibody preparations (30), and by the fact that neutrophil collagenase is stored within granules (31) while the macrophage enzyme is secreted without significant intracellular storage (7). Likewise, the collagenase inhibitor elaborated by undifferentiated U937 cells, whose expression is markedly increased by exposure to TPA, is a proven secretory product of alveolar macrophages (7) and is neither contained in nor released from neutrophils (8).…”

Section: Discussionmentioning

confidence: 99%

12-o-Tetradecanoyl-phorbol-13-acetate-differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and collagenase inhibitor accompany low levels of intracellular elastase and cathepsin G.

Welgus¹,

Connolly²,

Senior³

1986

J. Clin. Invest.

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Human monocytic tumor cells of the U937 cell line contain substantial quantities of two neutrophil neutral proteinases, elastase and cathepsin G, raising the question of whether their presence reflects an expression of transformation or whether normal monocytes undergo a developmental stage in which they produce certain neutrophil proteinases. To address this issue, we examined U937 cells for production of collagenase, since human alveolar macrophages release fibroblast-like collagenase, an enzyme that is distinct from neutrophil collagenase. Using an immunoassay that utilized antibody to skin fibroblast collagenase, we found that U937 cells secreted barely detectable quantities of enzyme, 10-12 ng/10' cells per 24 h, under basal conditions. Upon incubation with 10 nM 12-o-tetradecanoyl-phorbol-13-acetate (TPA), however, collagenase release increased 200-fold, comparable to the amount secreted by phorbol-stimulated human fibroblasts. Metabolic labeling and immunoprecipitation confirmed the enhanced synthesis of U937 cell collagenase upon TPA exposure. This enzyme activity further resembled fibroblast collagenase and differed from neutrophil collagenase by exhibiting preferential cleavage of monomeric type III collagen relative to type I. As previously observed with human alveolar macrophages, U937 cells also released a protein identical to the collagenase inhibitor produced by human skin fibroblasts, a molecule not associated with neutrophils. Release of this inhibitor increased 10-fold with TPA exposure.In contrast to collagenase and collagense inhibitor, TPAtreated U937 cells contained only 10-15% as much elastase and cathepsin G activities as control cells. Thus, TPA-induced differentiation modified the presence of these enzymes in the direction of their content in normal monocytes. Since the neutral proteinase profile of undifferentiated U937 cells resembles that of neutrophils and changes markedly after cellular differentiation to one that is characteristic of monocytes, these data suggest that neutrophilic proteinases may be produced by normal monocytes during the early stages of their differentiation.

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Section: Discussionmentioning

confidence: 99%

12-o-Tetradecanoyl-phorbol-13-acetate-differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and collagenase inhibitor accompany low levels of intracellular elastase and cathepsin G.

Welgus¹,

Connolly²,

Senior³

1986

J. Clin. Invest.

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“…An enzyme requiring Ca2+ or Mg2" was detected in bovine and human lens (Blow et al, 1975) and there have been several reports of a metaldependent 'gelatinase' in human neutrophil granulocytes (Harris & Krane, 1972;Sopata & Dancewicz, 1974;Murphy et al, 1977). Sapolsky et al (1976 and Nagase & Woessner (1977) have reported the detection of metallo-proteinases in human and bovine cartilage respectively.…”

Section: Discussionmentioning

confidence: 99%

Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes

Werb¹,

Dingle²,

Reynolds³

et al. 1978

Biochemical Journal

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A neutral proteinase secreted by rabbit synovial fibroblasts in parallel with specific collagenase was partially purified by ion-exchange chromatography. At pH 7.6 this proteinase degraded 35S-labelled bovine nasal proteoglycan and azo-casein. The enzymic activity was inhibited by EDTA, 1,10-phenanthroline and serum, whereas di-isopropyl phosphorofluoridate and soya-bean trypsin inhibitor had little effect. By gel filtration the apparent mol.wt. of the enzyme was 25000. The fibroblast neutral proteinase was compared with the proteoglycan-d. grading neutral proteinases of rabbit polymorphonuclear-leucocyte granules. Two distinct activities were found in the granules: one was inhibited by soya-bean trypsin inhibitor and the other by EDTA. The proteoglycandegrading proteinases of rabbit fibroblasts and polymorphonuclear leucocytes at acid pH also were examined. Both cathepsin D and a thiol-dependent proteinase contributed to the degradation of proteoglycan at pH4.5.

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“…The fibroblast proenzyme is secreted immediately after synthesis in vitro and in vivo (Nagase et al, 1983), and only a minor amount of the proenzyme is posttranslationally processed by glycosylation . In contrast, the neutrophil procollagenase is stored as a glycosylated protein within the specific granules ofthe neutrophils (Murphy et al, 1977;Knauper et al, 1990a). Secretion of the neutrophil proenzyme can be initiated by inflammatory mediators in vitro, which trigger the cells to secrete their metalloproteinases as inactive precursors (Hasty et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Direct activation of human neutrophil procollagenase by recombinant stromelysin

Knäuper

Wilhelm

Seperack

et al. 1993

Biochemical Journal

149

105

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Human neutrophil procollagenase was activated by incubation with recombinant active stromelysin. Activation was achieved by cleavage of the Gly78-Phe79 peptide bond at the end of the propeptide domain in a single-step activation mechanism. In addition, accelerated activation was achieved when N-terminally truncated, latent collagenase (with Phe49 as its N-terminal residue) was incubated with recombinant active stromelysin. Determination of the specific activity of recombinant-stromelysin-activated neutrophil collagenase with dinitrophenyl-octapeptide or type I collagen demonstrated the generation of high specific activity. The specific activity of stromelysin-activated enzyme was considerably higher than that of trypsin- or HgCl2-activated collagenase. Thus human neutrophil collagenase is superactivated, like the homologous fibroblast collagenase [Murphy, Cockett, Stephens, Smith and Docherty (1987) Biochem. J. 248, 265-268]. The occurrence of Phe79 at the N-terminus of the neutrophil collagenase seemed to be critical for superactivation, which is in agreement with data published by Suzuki, Enghild, Morodomi, Salvesen and Nagase [(1990) Biochemistry 29, 10261-10270] on fibroblast collagenase.

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Collagenase is a component of the specific granules of human neutrophil leucocytes

Cited by 161 publications

References 22 publications

12-o-Tetradecanoyl-phorbol-13-acetate-differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and collagenase inhibitor accompany low levels of intracellular elastase and cathepsin G.

12-o-Tetradecanoyl-phorbol-13-acetate-differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and collagenase inhibitor accompany low levels of intracellular elastase and cathepsin G.

Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes

Direct activation of human neutrophil procollagenase by recombinant stromelysin

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