Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis

作者：McGrath Rachel T; van den Biggelaar Maartje; Byrne Barry; O' Sullivan Jamie M; Rawley Orla; O' Kennedy Richard; Voorberg Jan; Preston Roger J S; O' Donnell James S

来源：Blood, 2013, 122(25): 4107-4110.

DOI：10.1182/blood-2013-04-496851

Platelet-von Willebrand factor (VWF) is stored within alpha-granules and accounts for similar to 20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (%26gt;50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation.

• 出版日期2013-12-12