Platelet-associated complement factor H in healthy persons and patients with atypical HUS.

Abstract:

:Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates that platelets are intimately involved in aHUS pathogenesis. It has been reported that a releasable pool of platelet CFH originates from alpha-granules. We observed that platelet CFH can arise from endogenous synthesis in megakaryocytes and that platelets constitutively lacking alpha-granules contain CFH. Electron and high-resolution laser fluorescence confocal microscopy revealed that CFH was present throughout the cytoplasm and on the surface of normal resting platelets with no evident concentration in alpha-granules, lysosomes, or dense granules. Therapeutic plasma transfusion in a CFH-null aHUS patient revealed that circulating platelets take up CFH with similar persistence of CFH in platelets and plasma in vivo. Washed normal platelets were also observed to take up labeled CFH in vitro. Exposure of washed normal platelets to plasma of an aHUS patient with CFH autoantibodies produced partial platelet aggregation or agglutination, which was prevented by preincubation of platelets with purified CFH. This CFH-dependent response did not involve P-selectin mobilization, indicating a complement-induced platelet response distinct from alpha-granule secretion.

journal_name

Blood

journal_title

Blood

authors

Licht C,Pluthero FG,Li L,Christensen H,Habbig S,Hoppe B,Geary DF,Zipfel PF,Kahr WH

doi

10.1182/blood-2009-03-205096

subject

Has Abstract

pub_date

2009-11-12 00:00:00

pages

4538-45

issue

20

eissn

0006-4971

issn

1528-0020

pii

blood-2009-03-205096

journal_volume

114

pub_type

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