Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration

Jo Ann Trial, Robert E. Baughn, James N. Wygant, Bradley W. McIntyre, Holly H. Birdsall, Keith A. Youker, Alida Evans, Mark L. Entman, Roger D. Rossen

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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 (α5β1 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 β1 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.

Original languageEnglish (US)
Pages (from-to)419-430
Number of pages12
JournalJournal of Clinical Investigation
Issue number4
StatePublished - Aug 1999

ASJC Scopus subject areas

  • Medicine(all)


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