Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration
JoAnn Trial, … , Mark L. Entman, Roger D. Rossen
JoAnn Trial, … , Mark L. Entman, Roger D. Rossen
Published August 15, 1999
Citation Information: J Clin Invest. 1999;104(4):419-430. https://doi.org/10.1172/JCI4824.
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Article

Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration

Abstract

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.

Authors

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

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Figure 4

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FN and FN fragments in cardiac lymph. (a) Cardiac lymph from a dog with ...
FN and FN fragments in cardiac lymph. (a) Cardiac lymph from a dog with ischemia-reperfusion injury. Lanes 1 and 2 (positive controls) show immunoblots of human plasma FN enriched for 40- and 120-kDa FN fragments, respectively. Lanes 3–8 show lymph collected 30–300 minutes after reperfusion. An arrow indicates 120-kDa FN fragments. Brackets indicate smaller FN fragments found in lymph 4–5 hours after reperfusion. (b) Cardiac lymph from an operated dog that, because of good collateral circulation, did not experience cardiac ischemia (lanes 1–6). Almost all FN remains in the native 220-kDa form. Lanes 7 and 8 show human FN enriched for 120- and 40-kDa FN fragments, respectively, to show that FN fragments could have been detected under the conditions of this experiment.