Modulation of fibronectin gene expression in human mononuclear phagocytes. Academic Article uri icon

Overview

MeSH

  • Adult
  • Female
  • Humans
  • Macrophages
  • Male
  • Middle Aged
  • Pulmonary Alveoli
  • Pulmonary Fibrosis
  • RNA, Messenger

MeSH Major

  • Fibronectins
  • Gene Expression Regulation
  • Monocytes

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 that 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.

publication date

  • December 1987

has subject area

  • Adult
  • Female
  • Fibronectins
  • Gene Expression Regulation
  • Humans
  • Macrophages
  • Male
  • Middle Aged
  • Monocytes
  • Pulmonary Alveoli
  • Pulmonary Fibrosis
  • RNA, Messenger

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC442445

Digital Object Identifier (DOI)

  • 10.1172/JCI113263

PubMed ID

  • 3680524

Additional Document Info

start page

  • 1720

end page

  • 1727

volume

  • 80

number

  • 6