Collagenolytic Activity in Gingivae of Man

Fullmer, Harold M.; Gibson, William A.

doi:10.1038/209728a0

Cited by 153 publications

(48 citation statements)

References 4 publications

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“…Several studies have demonstrated that elevated levels of collagenase and prostaglandins are found in chronic inflammatory lesions (1)(2)(3)(4)(5)(6)(7)(8)(9). High concentrations of prostaglandins and collagenase are secreted into the medium by isolated adherent rheumatoid synovial cells (18).…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin regulation of macrophage collagenase production.

Wahl¹,

Olsen²,

Sandberg³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

195

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The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibition of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0MgM PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2-to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 ,uM.PGF2, had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.Certain chronic inflammatory lesions are often accompanied by destruction of connective tissue. Increased levels of collagenase (1-6) and prostaglandins (779) have been identified in many of these lesions. The coexistence of these two components in sites of inflammation suggests that prostaglandins may influence collagenase production. Since we have previously shown that the macrophage, a prominent cell type in chronic inflammatory lesions, can be stimulated by endotoxin (10) or lymphokines (11) to produce collagenase, it was of interest to determine whether prostaglandins were involved in the activation of these cells. Here we report that the elevated levels of prostaglandin E2 (PGE2) produced by endotoxin-stimulated macrophages have a regulatory role in the production of collagenase by these cells. MATERIALS AND METHODSCulture Methods. Macrophages were obtained from mineral oil-induced peritoneal exudates in guinea pig and cultured as described (10). Activation of the macrophages was achieved by the addition of endotoxin (30 ,ug/ml) from Escherichia coli (055:B5 Difco Laboratories, Detroit, MI) to the cultures. Media were harvested daily from the cultures and frozen at -20°until assayed. Prostaglandins E1, E2, and F2a (PGE1, PGE2, and PGF2a) (generously supplied by John Pike, Upjohn Co., Kalamazoo, MI) were dissolved in ethanol and added to the culture The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. (12). One volume of 1 M sodium citrate (pH 3.5) was adde...

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Section: Resultsmentioning

confidence: 99%

Prostaglandin regulation of macrophage collagenase production.

Wahl¹,

Olsen²,

Sandberg³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

195

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“…Prior attempts to find a collagenase in normal or even osteoarthritic articular cartilage were probably unsuccessful because of the small quantity of enzyme present, its extralysosomal origin, and the presence of a high molecular weight inhibitor which made demonstration by the labeled collagen gel technique difficult. Subsequent studies have demonstrated collagenase activity in culture fluids of rat bone (6,14) and uterus (15,16), in human gingiva (17) and also bone (18), and skin (19) and synovia from patients with rheumatoid arthritis (20 Sakamoto (6,7) and used with slight modification in this study.…”

Section: Discussionmentioning

confidence: 99%

Collagenase and collagenase inhibitors in osteoarthritic and normal cartilage.

Ehrlich¹,

Mankin²,

Jones³

et al. 1977

J. Clin. Invest.

106

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A B S T R A C T In advanced osteoarthritis, all of the cartilaginous components are lost from the joint surface. Although mechanisms exist for proteoglycan degradation, there is not known to be any system for removal of the collagen. This study suggests that the loss of the collagen components may be a function of articular cartilage collagenase. The enzyme in normal human cartilage is bound to an inhibitor and appears to be present in very small amounts.Attempts to demonstrate collagenase activity in ground human articular cartilage or in its lysosomal fraction were unsuccessful. 7-Day cartilage tissue cultures also failed to demonstrate the presence of the enzyme; but the same culture fluid, incubated with trypsin, showed significant degradation of collagen, suggesting that trypsin destroyed the inhibitor.7-Day culture fluids were then chromatographed on a heparin-charged Sepharose 4B affinity column that had been activated with cyanogen bromide. This removed the inhibitor, and the chromatographed fluid from osteoarthritic cartilage released 42% of the incorporated counts of the collagen substrate, whereas normal cartilage released 10.1% and a trypsin control, 6.4%.Electrophoresis of the degradation products of the enzyme-collagen complex incubated at 37°C revealed breakdown was complete to small dialyzable fragments, while at 250C larger fragments were split off.

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“…Initial reports on collagenases in man came from studies of human gingiva and bone (Fulmer and Gibson, 1966). Together, these initial observations provided the basis for intense research that has led to the isolation and cloning of a continuously increasing number of matrix metalloproteinases (MMPs), now reaching approximately 28 (Table 1).…”

Section: (Ii) Matrix Metalloproteinases (A) General Aspectsmentioning

confidence: 99%

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Steffensen

Häkkinen

Larjava

2001

Critical Reviews in Oral Biology & Medicine

187

186

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During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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Collagenolytic Activity in Gingivae of Man

Cited by 153 publications

References 4 publications

Prostaglandin regulation of macrophage collagenase production.

Prostaglandin regulation of macrophage collagenase production.

Collagenase and collagenase inhibitors in osteoarthritic and normal cartilage.

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

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