RESUMEN
Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection.
Asunto(s)
Infecciones Bacterianas/inmunología , Plaquetas/inmunología , Animales , Bacterias/clasificación , Plaquetas/citología , Vasos Sanguíneos/lesiones , Vasos Sanguíneos/patología , Calcio/metabolismo , Movimiento Celular , Polaridad Celular , Humanos , Inflamación/inmunología , Integrinas/metabolismo , Ratones , Miosinas/metabolismo , Neutrófilos/citologíaRESUMEN
Von Willebrand factor (vWF), a glycoprotein in blood, mediates the adhesion of blood platelets and thus plays a crucial role in hemostasis and thrombosis. Functional coating of surfaces with vWF allows the investigation of in vitro adhesion of blood platelet. We used soft lithography to create a functional patterned substrate. vWF was printed on plasma-treated glass and mica surfaces, producing elongated network-like fibril structures. A minimum layer thickness of 3 nm was observed, corresponding to the height of a monolayer of vWF. The stability of the patterns was verified in a laminar fluid flow, and the bioactivity of the structures was tested with platelet adhesion experiments. Platelets adhered to and spread on printed vWF. These results indicate that printed vWF substrates are stable and functional in typical perfusion experiments, and thus provide a useful tool for studying thrombus formation in vitro.