Antiplatelet antibodies in WASP(-) mice correlate with evidence of increased in vivo platelet consumption

被引:31
作者
Marathe, Bindumadhav M. [2 ]
Prislovsky, Amanda [1 ]
Astrakhan, Alexander [3 ]
Rawlings, David J. [3 ,4 ,5 ]
Wan, Jim Y. [6 ]
Strom, Ted S. [1 ,2 ]
机构
[1] Memphis VA Med Ctr, Dept Pathol & Lab Med, 1030 Jefferson Ave, Memphis, TN 38104 USA
[2] Univ Tennessee, Ctr Hlth Sci, Dept Pathol & Lab Med, Memphis, TN 38163 USA
[3] Seattle Childrens Hosp Res Inst, Seattle, WA USA
[4] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA
[5] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA
[6] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA
基金
美国国家卫生研究院;
关键词
WISKOTT-ALDRICH-SYNDROME; X-LINKED THROMBOCYTOPENIA; SYNDROME PROTEIN; IMMUNOGLOBULIN-G; RECEPTOR; SPLENECTOMY; ACTIVATION; GENE; AUTOANTIBODIES; AUTOIMMUNITY;
D O I
10.1016/j.exphem.2009.08.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To study the role of antiplatelet antibodies in the thrombocytopenia of murine Wiskott-Aldrich syndrome (WAS). Materials and Methods. A flow cytometric method was developed for detection of serum antiplatelet antibodies via their binding to intact target platelets lacking surface antibodies. Platelets were labeled with 5-chloromethylfluorescein diacetate (CMFDA) in order to track their clearance from the circulation. WASP(-)mu MT(-/-) mice were generated by standard breeding methods. Results. Serum antiplatelet antibodies were detected in approximately 40% of WASP(-) males. The mean level of reticulated platelets is significantly increased in these antibody(+) males. While WASP(-) males show an approximately 50% reduction in platelet counts, 5% to 10% show a more severe thrombocytopenia associated with increased reticulated platelets, suggesting the presence of clearance-inducing antiplatelet antibodies. In support of that inference, 90% of the latter mice show detectable serum antiplatelet antibodies. The antibodies are primarily immunoglobulin G, and are also detected in > 30% of CD47(-/-) males. WASP(-mu MT(-/-) males, which demonstrate no serum- or platelet-associated antibodies, show a degree of thrombocytopenia similar to that of WASP(-) males. Their platelet clearance rates remain accelerated-more so in WASP(-)mu MT(-/-) than WASP(+)mu MT(-/-) recipients. Conclusions. These findings suggest that platelet WASP deficiency results in an increase in platelet clearance rates by two mechanisms: an antibody-independent mechanism that largely requires WASP deficiency in trans, and an anti body-dependent mechanism that does not. Both an increased incidence of antiplatelet antibodies and an increased susceptibility to their effects contribute to anti body-dependent clearance of WASP(-) platelets. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:1353 / 1363
页数:11
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