title: Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia.
abstract: Immune thrombocytopenic purpura (ITP) is a haematological disorder characterized by increased platelet consumption. The destruction of platelets is mediated by the reticulo-endothelial system (RES), particularly by splenic and hepatic macrophages. Previously, we demonstrated in a mouse model of thrombocytopenia that the depletion of these cells by liposome-encapsulated clodronate (LIP-CLOD) induces the recovery of the platelet count. We now report that LIP-CLOD is capable of reversing the thrombocytopenia with minimal effects on both, functional RES integrity and platelet functionality. Our data indicate that thrombocytopenic mice treated with low doses of LIP-CLOD/body weight increase the platelet count to haemostatically safe values within 18 h of treatment. The predictable bleeding time was significantly decreased in these mice, suggesting that the circulating platelets have enhanced haemostatic capacity. Platelet functionality measured through the ADP-induced fibrinogen-binding assay showed normal platelet activation after treatment. Regarding immunological competence, mice treated with LIP-CLOD showed similar antibody titres against sheep red blood cells. However, antibody-dependent cell-mediated cytotoxicity carried out by splenocytes was reduced. All these data demonstrate that LIP-CLOD deserves consideration as a potential therapeutic approach in thrombocytopenic states in which the rapid increase of platelet count is the primary goal.
authors.affiliation: División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Alves-Rosa
authors.forename: Carmen
authors.initials: C
authors.lastname: Stanganelli
authors.forename: Juana
authors.initials: J
authors.lastname: Cabrera
authors.forename: Dora
authors.initials: D
authors.lastname: Cymberknop
authors.forename: Carolina
authors.initials: C
authors.lastname: Rubel
authors.forename: Silvia
authors.initials: S
authors.lastname: Vanzulli
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Marina
authors.initials: M
authors.lastname: Palermo
authors.forename: Martín A
authors.initials: MA
authors.lastname: Isturiz
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D004002:Clodronic Acid / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008081:Liposomes; D008297:Male; D051379:Mice; D023421:Models, Animal; D010587:Phagocytosis / Q000187:drug effects; D015539:Platelet Activation; D010976:Platelet Count; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy*
chemical_list: D000963:Antimetabolites; D008081:Liposomes; D004002:Clodronic Acid