Abstract | OBJECTIVE: 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(-)muMT(-/-) 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(-)muMT(-/-) 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(-)muMT(-/-) than WASP(+)muMT(-/-) 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 antibody-dependent mechanism that does not. Both an increased incidence of antiplatelet antibodies and an increased susceptibility to their effects contribute to antibody-dependent clearance of WASP(-) platelets.
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Authors | Bindumadhav M Marathe, Amanda Prislovsky, Alexander Astrakhan, David J Rawlings, Jim Y Wan, Ted S Strom |
Journal | Experimental hematology
(Exp Hematol)
Vol. 37
Issue 11
Pg. 1353-63
(Nov 2009)
ISSN: 1873-2399 [Electronic] Netherlands |
PMID | 19733207
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Autoantibodies
- CD47 Antigen
- Cd47 protein, mouse
- Opsonin Proteins
- Was protein, mouse
- Wiskott-Aldrich Syndrome Protein
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Topics |
- Animals
- Autoantibodies
(immunology)
- Autoimmune Diseases
(blood, genetics, immunology, pathology)
- Blood Platelets
(immunology)
- Bone Marrow
(pathology)
- CD47 Antigen
(genetics, physiology)
- Male
- Mice
- Mice, Knockout
- Models, Animal
- Opsonin Proteins
(immunology)
- Phagocytosis
(immunology, physiology)
- Platelet Count
- Spleen
(pathology)
- Splenomegaly
(etiology, pathology)
- Wiskott-Aldrich Syndrome
(blood, genetics, immunology, pathology)
- Wiskott-Aldrich Syndrome Protein
(deficiency)
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