title: Increased uptake by splenic red pulp macrophages contributes to rapid platelet turnover in WASP(-) mice.
abstract: Thrombocytopenia caused by rapid platelet consumption contributes to the severe thrombocytopenia of Wiskott-Aldrich syndrome (WAS) and to the milder thrombocytopenia seen in murine WAS. We show that rapid clearance of ¹¹¹In-labeled murine WASP(-) platelets correlates with enhanced splenic uptake. Using platelets labeled with a pH-sensitive fluorescent marker (pHrodo), we quantify normal platelet uptake by red pulp macrophages (RPMs), and demonstrate its enhancement after in vivo opsonization of platelets. The spleens of WASP(-) mice contain an increased number of RPM, and rapid clearance of WASP(-) platelets in WASP(-) mice in turn generates an increased number of pHrodo(+) splenic RPMs. To separately assess the platelet intrinsic and recipient-dependent functions involved in the clearance and splenic phagocyte uptake of WASP(-) platelets, we performed "crossed" pHrodo(+) platelet injection studies (wild type [WT] to WASP(-), WASP(-) to WT). We show that an extrinsic effect of recipient WASP deficiency on the clearance of WASP(-) platelets correlates with increased platelet uptake by RPMs. An intrinsic effect of platelet WASP deficiency on platelet clearance does not, however, correlate with increased total uptake by WT or WASP(-) RPMs. In contrast to other published findings, we find no evidence of a baseline or antibody-induced increase in phosphatidyl serine exposure on WASP(-) platelets. Our findings suggest that an increased number of RPMs in WASP(-) mice contributes significantly to the increased platelet consumption rate in WASP(-) mice. This might explain the consistent efficacy of splenectomy in murine and clinical WAS.
authors.affiliation: Department of Pathology and Laboratory Medicine, Memphis Veterans Administration Medical Center, Memphis, TN, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Prislovsky
authors.forename: Ted S
authors.initials: TS
authors.lastname: Strom
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D013921:Thrombocytopenia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein