Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration.
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.
Trial
J
J
Immunology Research Laboratory and the Research Center for AIDS and HIV-Related Infections, Houston Veterans Affairs Medical Center, Department of Medicine, Baylor College of Medicine, Texas 77030, USA. jtrial@bcm.tmc.edu
Baughn
R E
RE
Wygant
J N
JN
McIntyre
B W
BW
Birdsall
H H
HH
Youker
K A
KA
Evans
A
A
Entman
M L
ML
Rossen
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004285:Dogs; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008196:Lymph / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D017469:Receptors, Fibronectin / Q000378:metabolism*
D005353:Fibronectins; D010446:Peptide Fragments; D017469:Receptors, Fibronectin