Experimental hematology · 2009
Antiplatelet antibodies in WASP(-) mice correlate with evidence of increased in vivo platelet consumption.
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Marathe Bindumadhav M, Prislovsky Amanda, Astrakhan Alexander, Rawlings David J, Wan Jim Y, Strom Ted S
Аннотация
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(-)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.
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.