Submitted February 6, 2006
Accepted May 16, 2006
Impact of fibronectin assembly on platelet thrombus formation in response to type I collagen and von Willebrand factor
Jaehyung Cho and Deane F Mosher*
Molecular & Cellular Pharmacology Program, University of Wisconsin-Madison School of Medicine,USA
* Corresponding author; email: dfmosher{at}wisc.edu.
Plasma fibronectin enhances platelet thrombus formation on surfaces coated with collagen. We investigated the role of fibronectin assembly in this process. Platelets adherent to fibrillar type I collagen, but not platelets adherent to von Willebrand factor (vWF), supported assembly of plasma fibronectin under static conditions. At a shear rate of 1,250/s-1, platelets adherent to collagen assembled co-perfused plasma fibronectin and formed larger thrombi in a fibronectin-concentration dependent manner, with a maximum effect at 250 µg/ml. Enhanced thrombus formation on collagen was blocked by a peptide that binds to the N-terminal region of fibronectin and inhibits fibronectin assembly. Crosslinking of fibronectin to collagen prior to exposure to platelets had no effect on thrombus formation. Collagen-induced platelet thrombus formation at a shear rate of 5,000/s-1 required co-perfusion with vWF and did not result in assembly of co-perfused fibronectin. vWF-mediated increase in platelet thrombi on collagen was not enhanced and indeed was somewhat attenuated by co-perfused fibronectin at a shear rate of 5,000/s-1. These results indicate that, at moderately high but not very high shear rates, fibronectin assembly in platelet aggregates forming in response to collagen enhances thrombus formation and serves as an alternative to vWF-mediated enhancement.
