Rapid recovery of platelet count following administration of liposome-encapsulated clodronate in a mouse model of immune thrombocytopenia.
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.
Alves-Rosa
Fernanda
F
División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Stanganelli
Carmen
C
Cabrera
Juana
J
Cymberknop
Dora
D
Rubel
Carolina
C
Vanzulli
Silvia
S
van Rooijen
Nico
N
Palermo
Marina
M
Isturiz
Martín A
MA
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*
D000963:Antimetabolites; D008081:Liposomes; D004002:Clodronic Acid