Platelet reactions in the non-self recognition of material surfaces
Sammanfattning
Every material introduced into the body in order to function in contact with a living tissue is defined as a biomaterial. Biomaterials are used throughout the world in an increasing rate to replace and augment organ functions. The insertion of an implant into the human body will initiate blood coagulation at the surface of the material.After water and electrolytes have adhered to the surface a protein film starts to form. Platelets appear at the surface after a few seconds and the contact between platelets and the protein film is one of the initial steps in the non-self recognition of a foreign material.The adhesion and reactions of platelets were investigated using both whole blood and isolated platelets. The platelets were isolated by a new method, where a reversible inhibition of platelet function was achieved by magnesium ions. The binding of platelets to the surface, their spreading, exposure of P-selectin, and release of granular contents were investigated.The results show that the initial platelet adhesion to both hydrophilic and hydrophobic surfaces is mediated by the fibrinogen receptor GPIIb/IIIa. The binding of von Willebrand factor and exposure of P-selectin on the platelet surface are thrombin dependent events, but the spreading of platelets is not. Different protein coatings were seen to generate different responses from platelets. IgG was seen to fragmentize adherent platelets, leaving surface bound micro particles, while von Willebrand factor was seen to induce exposure of P-selectin on the platelet surface. The exposure of P-selectin on the platelet surface is of importance for the subsequent signalling between platelets and neutrophils, as neutrophils are known to bind to P-selectin. The release of granules, both a- and dense, was highest for platelets adhering to IgG and thrombin coated surfaces. Neither of these proteins was seen to have the same effects when added in soluble form to fibrinogen adherent platelets.In conclusion, the initial platelet adhesion to surfaces in contact with blood is mediated by fibrinogen but the presence of other proteins in the film, as for example IgG and von Willebrand factor, generates very different platelet responses.
Universitet
Göteborgs universitet/University of Gothenburg
Institution
Institute of anatomy and cell biology
Institutionen för anatomi och cellbiologi
Disputation
Hörsal Ivan Ivarsson, Anatomi och Cellbiologi, Medicinaregatan 3B kl 09.00
Datum för disputation
2001-06-01
Fil(er)
Datum
2001Nyckelord
platelet
biomaterial
adhesion
granule
P-selectin
plasma protein
blood
activation
release
Publikationstyp
Doctoral thesis
ISBN
91-628-4763-5