Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G

Okada, Yasunori; Nakanishi, Isao

doi:10.1016/0014-5793(89)80657-x

Cited by 165 publications

(95 citation statements)

References 22 publications

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“…When no APMA was added, no MMP activity could be detected, indicating that macrophages secreted only latent MMPs. Enzymes that are secreted in an active form, such as elastase and cathepsin G secretion by neutrophils, may be responsible for the activation of latent MMPs (51). Furthermore, oxygen radical production by macrophages results in reactive species that are capable of activating latent MMPs (52).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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Objective. To evaluate Fc␥ receptor (Fc␥R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc␥RI, Fc␥RII, and Fc␥RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation.Methods. Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc␥R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF␣, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc␥RI, Fc␥RII, and Fc␥RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/ collagenases was measured by degradation of fluorescent gelatin.Results. Immunohistochemistry showed higher Fc␥RII and Fc␥RIII expression in RA synovium than in controls. Fc␥RII and Fc␥RIII, but not Fc␥RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF␣ expression correlated positively with Fc␥RIII expression. Moreover, MMP-1 expression strongly correlated with Fc␥R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc␥RII and Fc␥RIII compared with controls. Twentyfour hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF␣ and gelatinase/collagenase was measured.Conclusion. RA synovium and mature RA macrophages express significantly elevated levels of Fc␥RII and Fc␥RIII, resulting in much higher production of TNF␣ and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc␥R on mature synovial macrophages is involved in the pathology of RA.

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Section: Discussionmentioning

confidence: 99%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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“…21 Similarly, high elastase levels have been observed in chronic wounds. 22,23 Interestingly, elastase can also activate other classes of proteases (i.e., MMPs) [24][25][26] and inactivate protease inhibitors, 27 which could increase the total protease activity in a wound and further exacerbate host tissue damage. Elastase can also cleave and inactivate growth factors, such as hepatocyte growth factor, which becomes ineffective at stimulating keratinocyte migration after cleavage.…”

Section: Neutrophil-derived Proteasesmentioning

confidence: 99%

Neutrophils and Wound Repair: Positive Actions and Negative Reactions

Wilgus

Roy

McDaniel

2013

Advances in Wound Care

447

356

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“…Multiple mechanisms are capable of initiating the cleavage events, including other proteolytic enzymes. Heat and mercurial agents (e.g., 4-amino-phenylmercuric acetate) are also able to trigger the conversion process via an auto-proteolytic pathway (Okada et al, 1988;Okada & Nakanashi, 1989;Nagase et al, 1990;Koklitis et al, 1991). However, the positions and conformations of the active site residues are unchanged during conversion.…”

Section: Pro-stromelysin-1mentioning

confidence: 99%

Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes

1998

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Proteolytic enzymes are synthesized as inactive precursors, or "zymogens," to prevent unwanted protein degradation, and to enable spatial and temporal regulation of proteolytic activity. Upon sorting or appropriate compartmentalization, zymogen conversion to the active enzyme typically involves limited proteolysis and removal of an "activation segment." The sizes of activation segments range from dipeptide units to independently folding domains comprising more than 100 residues. A common form of the activation segment is an N-terminal extension of the mature enzyme, or "prosegment," that sterically blocks the active site, and thereby prevents binding of substrates. In addition to their inhibitory role, prosegments are frequently important for the folding, stability, and/or intracellular sorting of the zymogen. The mechanisms of conversion to active enzymes are diverse in nature, ranging from enzymatic or nonenzymatic cofactors that trigger activation, to a simple change in pH that results in conversion by an autocatalytic mechanism. Recent X-ray crystallographic studies of zymogens and comparisons with their active counterparts have identified the structural changes that accompany conversion. This review will focus upon the structural basis for inhibition by activation segments, as well as the molecular events that lead to the conversion of zymogens to active enzymes.

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Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G

Cited by 165 publications

References 22 publications

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Neutrophils and Wound Repair: Positive Actions and Negative Reactions

Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes

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