Fibrillar cellular fibronectin supports efficient platelet aggregation and procoagulant activity.
The ability of cellular fibronectin, found in the vessel wall in a fibrillar conformation, to regulate platelet functions and trigger thrombus formation remains largely unknown. In this study, we evaluated how parietal cellular fibronectin can modulate platelet responses under flow conditions. A fibrillar network was formed by mechanically stretching immobilised dimeric cellular fibronectin. Perfusion of anticoagulated whole blood over this surface resulted in efficient platelet adhesion and thrombus growth. The initial steps of platelet adhesion and activation, as evidenced by filopodia extension and an increase in intracellular calcium levels (419 ± 29 nmol/l), were dependent on integrins α5β1 and αIIbβ3. Subsequent thrombus growth was mediated by these integrins together with the GPIb-V-IX complex, GPVI and Toll-like receptor 4. The involvement of Toll-like receptor 4 could be conveyed via its binding to the EDA region of cellular fibronectin. Upon thrombus formation, the platelets became procoagulant and generated fibrin as revealed by video-microscopy. This work provides evidence that fibrillar cellular fibronectin is a strong thrombogenic surface which supports efficient platelet adhesion, activation, aggregation and procoagulant activity through the interplay of a series of receptors including integrins α5β1 and αIIbβ3, the GPIb-V-IX complex, GPVI and Toll-like receptor 4.
['Maurer|Eric|E|', 'Schaff|Mathieu|M|', 'Receveur|Nicolas|N|', 'Bourdon|Catherine|C|', 'Mercier|Luc|L|', 'Nieswandt|Bernhard|B|', 'Dubois|Christophe|C|', 'Jandrot-Perrus|Martine|M|', 'Goetz|Jacky G|JG|', 'Lanza|François|F|', 'Gachet|Christian|C|', 'Mangin|Pierre H|PH|']
D000818:Animals D017304:Annexin A5 D001777:Blood Coagulation D005109:Extracellular Matrix D005337:Fibrin D005347:Fibroblasts D005353:Fibronectins D055767:Immobilized Proteins D019012:Integrin beta1 D016023:Integrins D056656:Lab-On-A-Chip Devices D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D046210:Microfluidic Analytical Techniques D008855:Microscopy, Electron, Scanning D010973:Platelet Adhesiveness D010974:Platelet Aggregation D040201:Platelet Membrane Glycoprotein IIb D010980:Platelet Membrane Glycoproteins D012212:Rheology D013314:Stress, Mechanical D051197:Toll-Like Receptor 4
fibronectin Platelets arterial thrombosis haemostasis