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

Respiratory Research

Stephen I Rennard³  Ronald F Ertl³  Fu-Qiang Wen³  Tadashi Kohyama³  Hangjun Wang¹  C Magnus Sköld²  Xiangde Liu³  Yunkui Zhu³ 

[1] Mount Sinai Hospital, Pathology and Laboratory Medicine, Toronto, Ontario, Canada;Karolinska Hospital, Stockholm, Sweden;University of Nebraska Medical Center, Omaha, Nebraska, USA

关键词: prostaglandin E₂;    monocytes;    metalloproteinases;    lung fibroblasts;    collagen degradation;   

Others  :  1227426
DOI  :  10.1186/rr73

 received in 2001-03-05, accepted in 2001-08-08,  发布年份 2001

【 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.

【 授权许可】

   
2001 Zhu etal, licensee BioMed Central Ltd

【 图 表 】

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