Modulation of fibronectin gene expression in human mononuclear phagocytes

K. Yamauchi, Y. Martinet, Ronald Crystal

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Under some conditions, mononuclear phagocytes spontaneously synthesize and release fibronectin, an extracellular matrix glycoprotein with versatile effects on cell-matrix interactions. To gain insight into the processes that modulate the level of fibronectin secretion by these cells, we used monocytes, in vitro matured monocytes and alveolar macrophages as models to compare fibronectin mRNA levels and fibronectin secretion in a variety of circumstances. Using Northern analysis and dot-blot analysis with a 32P-labeled human fibronectin cDNA probe, we evaluated steady-state mRNA levels and a human fibronectin-specific ELISA was used to evaluate fibronectin secretion. In all cases the amounts of fibronectin secreted paralleled fibronectin mRNA levels. Specifically (a) when fibronectin mRNA was undetectable, as in the case of normal blood monocytes, no fibronectin was secreted, but whenever fibronectin mRNA was present, as in normal alveolar macrophages, fibronectin was secreted by the cells; (b) as monocytes matured into macrophages in vitro, the cells began to express fibronectin mRNA and the cells secreted fibronectin; (c) when alveolar macrophages were activated with surface stimuli such as lipopolysaccharide (LPS) or immune complexes, fibronectin mRNA levels decreased and in parallel, the cells secreted less fibronectin; (d) in idiopathic pulmonary fibrosis (IPF), alveolar macrophages contained severalfold more fibronectin mRNA transcripts than normal and the cells spontaneously secreted severalfold more fibronectin than normal; and (e) when IPF alveolar macrophages were placed in culture the fibronectin mRNA levels in the cells decreased with time, and concurrently the amounts of fibronectin produced per unit time continually decreased. The observation of a strict concordance of fibronectin mRNA levels and fibronectin release by mononuclear phagocytes suggests that, at least in many circumstances, fibronectin secretion by mononuclear phagocytes is controlled by steady-state levels of fibronectin mRNA.

Original languageEnglish
Pages (from-to)1720-1727
Number of pages8
JournalJournal of Clinical Investigation
Volume80
Issue number6
DOIs
Publication statusPublished - 1 Jan 1987
Externally publishedYes

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Phagocytes
Fibronectins
Gene Expression
Messenger RNA
Alveolar Macrophages
Monocytes
Idiopathic Pulmonary Fibrosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Modulation of fibronectin gene expression in human mononuclear phagocytes. / Yamauchi, K.; Martinet, Y.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 80, No. 6, 01.01.1987, p. 1720-1727.

Research output: Contribution to journalArticle

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