Collaborative interactions between neutrophil elastase and metalloproteinases in extracellular matrix degradation in three dimensional collagen gels

被引：37

作者：

Zhu Y. ^{[1
]}

Liu X. ^{[1
]}

Sköld C.M. ^{[2
]}

Wang H. ^{[3
]}

Kohyama T. ^{[1
]}

Wen F.-Q. ^{[1
]}

Ertl R.F. ^{[1
]}

Rennard S.I. ^{[1
]}

机构：

[1] University of Nebraska Medical Center, Omaha, NE

[2] Karolinska Hospital, Stockholm

[3] Mount Sinai Hospital, Pathology and Laboratory Medicine, Toronto, Ont.

来源：

Respiratory Research | / 2卷 / 5期

关键词：

Collagen degradation; Lung fibroblasts; Metalloproteinases; Monocytes; Prostaglandin E[!sub]2[!/sub;

D O I：

10.1186/rr73

中图分类号：

学科分类号：

摘要：

Background: Extended culture of monocytes and fibroblasts in three-dimensional collagen gels leads to degradation of the gels (see linked study in this issue, "Fibroblasts and monocytes contract and degrade three-dimensional collagen gels in extended co-culture"). The current study, therefore, was designed to evaluate production of matrix-degrading metalloproteinases by these cells in co-culture and to determine if neutrophil elastase could collaborate in the activation of these enzymes. Since co-cultures produce prostaglandin E2 (PGE2), the role of PGE2 in this process was also evaluated. Methods: Blood monocytes from healthy donors and human fetal lung fibroblasts were cast into type I collagen gels and maintained in floating cultures for three weeks. Matrix metalloproteinases (MMPs) were assessed by gelatin zymography (MMPs 2 and 9) and immunoblotting (MMPs 1 and 3). The role of PGE2 was explored by direct quantification, and by the addition of exogenous indomethacin and/or PGE2. Results: Gelatin zymography and immunoblots revealed that MMPs 1, 2, 3 and 9 were induced by co-cultures of fibroblasts and monocytes. Neutrophil elastase added to the medium resulted in marked conversion of latent MMPs to lower molecular weight forms consistent with active MMPs, and was associated with augmentation of both contraction and degradation (P<0.01). PGE2 appeared to decrease both MMP production and activation. Conclusion: The current study demonstrates that interactions between monocytes and fibroblasts can mediate tissue remodeling.

引用

页码：300 / 305

页数：5

共 32 条

[1]

Grinnell F., Fibroblasts, myofibroblasts and wound contraction, J. Cell. Biol., 124, pp. 401-404, (1994)

[2]

Bell E., Ivarsson B., Merrill C., Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro, Proc. Natl. Acad. Sci. USA, 76, pp. 1274-1278, (1979)

[3]

Skold C.M., Liu X.D., Umino T., Zhu Y.K., Ertl R.F., Romberger D.J., Rennard S.I., Blood monocytes attenuate lung fibroblast contraction of three-dimensional collagen gels in coculture, Am. J. Physiol. Lung Cell. Mol. Physiol., 279, (2000)

[4]

Skold C.M., Liu X., Umino T., Zhu Y., Ohkuni Y., Romberger D.J., Spurzem J.R., Heires A.J., Rennard S.I., Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels, Am. J. Respir. Crit. Care Med., 159, pp. 1138-1146, (1999)

[5]

Zhu Y.K., Skold C.M., Liu X.D., Wang H., Kohyama T., Wen F.Q., Ertl R.F., Rennard S.I., Fibroblasts and monocytes contract and degrade three-dimensional collagen gels in extended culture, Respir. Res., 2, pp. 295-299, (2001)

[6]

Thurlbeck W.M., Muller N.L., Emphysema: Definition, imaging, and quantification, AJR Am. J. Roentgenol., 163, pp. 1017-1025, (1994)

[7]

Senior R.M., Tegner H., Kuhn C., Ohlsson K., Starcher B.C., Pierce J.A., The induction of pulmonary emphysema with human leukocyte elastase, Am. Rev. Resp. Dis., 116, pp. 469-475, (1977)

[8]

Liu Z., Zhou X., Shapiro S.D., Shipley J.M., Twining S.S., Diaz L.A., Senior R.M., Werb Z., The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo, Cell., 102, pp. 647-655, (2000)

[9]

Mio T., Adachi Y., Romberger D.J., Ertl R.F., Rennard S.I., Regulation of fibroblast proliferation in three dimensional collagen gel matrix, In Vitro Cell. Dev. Biol., 32, pp. 427-433, (1996)

[10]

Zhang Y., McCluskey K., Fujii K., Wahl L.M., Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha, granulocyte-macrophage CSF, and IL-1 beta through prostaglandin-dependent and -independent mechanisms, J. Immunol., 161, pp. 3071-3076, (1998)

← 1 2 3 4 →