Modulation of platelet caspases and life-span by anti-platelet antibodies in mice.
Anti-platelet antibodies are known to contribute to some types of thrombocytopenia. In this work we investigated anti-platelet antibodies with opposite influence upon activation and kinetics of platelet caspases. A rabbit anti-platelet antibody induced a profound thrombocytopenia, which was associated with an increase of microparticles in plasma and an activation of platelet caspases, as detected by the binding of a carboxyfluorescein-labeled fluoromethyl ketone probe (FAM-VAD-fmk). Furthermore, microparticles and thrombocytopenia were prevented by the injection of a caspase inhibitor ZVAD-fmk. In contrast, an anti-CD18 mAb (M18.2) induced a thrombocytosis, due to an increased platelet life-span and which was evident in wild-type (+/+), but not in CD18-/- or CD87-/-, mice indicating a requirement of these two surface molecules. Activation of caspases was decreased in platelets from mice injected with the M 18.2 mAb, as evidenced by a decreased binding of the VAD probe, detected by flow cytometry, or an increase in the level of pro-caspase-3, seen on Western blots. These observations indicate firstly, that anti-platelet antibodies can either promote or inhibit activation of platelet caspases, and secondly, that the activation of caspases regulates platelet life-span.
Piguet
Pierre F
PF
Department of Pathology, University of Geneva, 1 rue M. Servet, CW 1211 Geneva, Switzerland. pierre.piguet@medecine.unige.ch
Vesin
Christian
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010975:Platelet Aggregation Inhibitors / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D013921:Thrombocytopenia / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D010975:Platelet Aggregation Inhibitors; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D018799:Intercellular Adhesion Molecule-1; D020169:Caspases