Colchicine suppresses the release of fibroblast growth factors from alveolar macrophages in vitro. The basis of a possible therapeutic approach to the fibrotic disorders

S. I. Rennard, P. B. Bitterman, T. Ozaki, W. N. Rom, Ronald Crystal

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Fibrosis is the accumulation of fibroblasts and the connective tissue products secreted by these cells, usually subsequent to tissue injury. While fibrosis can be useful in preserving the general structural integrity of a tissue, it often alters cell-cell and cell-connective tissue interactions, which leads to loss of tissue function. On the basis of the concept that mononuclear phagocytes can direct the development of fibrosis through the release of specific mediators that stimulate fibroblast proliferation, we propose a therapeutic strategy to prevent fibrosis by preventing the release of these specific mediators. The present study demonstrated that colchicine, a widely used and well-tolerated drug, can block alveolar macrophage release of 2 mediators associated with the development of fibrosis in interstitial lung disease, fibronectin, and the alveolar-macrophage-derived growth factor (AMDGF). Colchicine blocked the spontaneous release of fibronectin by alveolar macrophages obtained from patients with fibrotic lung disease by 23 ± 4% after 24 h and by greater than 90% after 72 h. AMDGF release was blocked by 68 ± 10% after 4 h (p<0.01, all comparisons). The effect of colchicine was not due to nonspecific toxicity since [14C]proline tracer studies demonstrated that macrophages treated with colchicine were capable of de novo protein synthesis and the secretion of several protein products, despite the fact that fibronectin and AMDGF release were suppressed. The effect of colchicine on the spontaneous release of both fibronectin and AMDGF could be observed at concentrations less than 10 ng/ml, levels that can be achieved in vivo. These results suggest that one component of therapeutic strategies for prevention of the development of interstitial fibrosis might be directed toward inhibition of the release of mononuclear phagocyte mediators that stimulate fibroblast proliferation.

Original languageEnglish
Pages (from-to)181-185
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume137
Issue number1
DOIs
Publication statusPublished - 1 Jan 1988
Externally publishedYes

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Fibroblast Growth Factors
Alveolar Macrophages
Colchicine
Fibrosis
Fibronectins
Fibroblasts
Phagocytes
Therapeutics
Connective Tissue Cells
Interstitial Lung Diseases
Proline
Connective Tissue
Lung Diseases
In Vitro Techniques
Proteins
Macrophages
alveolar macrophage growth factor
Wounds and Injuries
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Colchicine suppresses the release of fibroblast growth factors from alveolar macrophages in vitro. The basis of a possible therapeutic approach to the fibrotic disorders. / Rennard, S. I.; Bitterman, P. B.; Ozaki, T.; Rom, W. N.; Crystal, Ronald.

In: American Review of Respiratory Disease, Vol. 137, No. 1, 01.01.1988, p. 181-185.

Research output: Contribution to journalArticle

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