Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration

J Clin Invest. 1999 Aug;104(4):419-30. doi: 10.1172/JCI4824.


To identify the mechanisms that cause monocyte localization in infarcted myocardium, we studied the impact of ischemia-reperfusion injury on the surface expression and function of the monocyte fibronectin (FN) receptor VLA-5 (alpha(5)beta(1) integrin, CD49e/CD29). Myocardial infarction was associated with the release of FN fragments into cardiac extracellular fluids. Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments. Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin. We postulated that changes in VLA-5 expression, which were induced by interactions with cell-binding FN fragments, may alter monocyte migration into tissue FN, a prominent component of the cardiac extracellular matrix. Support for this hypothesis came from experiments showing that FN120 treatment significantly reduced both spontaneous and MCP-1-induced monocyte migration on an FN-impregnated collagen matrix. In vivo, it is likely that contact with cell-binding FN fragments also modulates VLA-5/FN adhesive interactions, and this causes monocytes to accumulate at sites where the fragment concentration is sufficient to ensure proteolytic degradation of VLA-5.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Movement / drug effects
  • Dogs
  • Extracellular Matrix / physiology
  • Fibronectins / chemistry
  • Fibronectins / physiology*
  • Humans
  • In Vitro Techniques
  • Lymph / physiology
  • Molecular Sequence Data
  • Monocytes / drug effects*
  • Monocytes / pathology
  • Monocytes / physiology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Receptors, Fibronectin / metabolism*


  • Fibronectins
  • Peptide Fragments
  • Receptors, Fibronectin