ABSENCE OF INCORPORATION OF PLASMA VON-WILLEBRAND-FACTOR INTO PORCINEPLATELET ALPHA-GRANULES

In order to study the relationship between plasma and platelet von Wil lebrand factor (vWF), we used an experimental model of crossed bone ma rrow transplantation (BMT) between SLA immunocompatible normal and hom ozygous von Willebrand (vWD) pigs. A normal pig received bone marrow f rom a vWD pig and a second pig with vWD was engrafted with marrow from a normal pig. Each recipient, after total irradiation of 10 Grays, re ceived by a central catheter 10(10) monocellular bone marrow cells wit hout immunosuppression. The animals were followed for 50 d and no graf t rejection or graft-versus-host disease was observed. After aplasia o ccurring 3 weeks after BMT, white blood cells and platelets returned t o normal. Before transplantation, in the vWD pig, vWFAg and vWF activi ty were not detected in plasma and in platelet and megakaryocyte alpha -granules, After transplantation with normal marrow, platelet vWFAg an d platelet vWF activity were normal and high molecular weight multimer s and numerous tubular structures were present in alpha-granules. Befo re transplantation, the normal pig had normal plasma and platelet vWFA g-vWF activity, normal multimeric pattern, and the platelet and megaka ryocyte alpha-granules displayed many tubular structures, eccentricall y located in one of their poles, coinciding with immunogold staining v WFAg. After transplantation with homozygous vWD marrow, platelet and m egakaryocyte alpha-granules lacked tubular structures. Alpha-granule i mmunogold staining for vWF was consistently negative, although plasma vWF was at a normal level. In conclusion, this study shows that, unlik e other plasma proteins such as fibrinogen, vWF endocytosis does not o ccur from plasma to the platelet alpha-granules, Platelet and megakary ocyte vWF solely originates from megakaryocyte endogenous synthesis an d is independent of plasma vWF.