Antiphospholipid antibodies in an in vivo thrombosis model in mice.
The mouse model described in this study offers a unique method of determining the characteristics and mechanism(s) of action of aCL antibodies in thrombosis in vivo. In addition, this animal model enables the study of the kinetics of formation and dissolution of thrombus, as well as clot area, to be studied in a dynamic fashion. Other models for evaluation of thrombus formation rely on measurements of thrombus size and weight in ligated vessel segments where flow may be interrupted artificially. In addition, two important findings can be extracted from the study. (1) The size of the thrombi were significantly larger in mice that were passively immunized with IgG-APS (four patient samples examined) and with IgM-APS (two patient samples examined) compared with mice injected with saline or with immunoglobulin from control patients. (2) The clot persisted significantly for longer periods of time (total time) in animals injected with IgG-APS or IgM-APS when compared with control animals. Based on in vitro experiments, it is possible that these antibodies may inhibit protein C activation, neutralize the inhibitory activity action of beta 2 glycoprotein I (beta 2GPI), or activate platelets at the site of the femoral vein injury. Because this model enables to study the dynamics of thrombus formation, it is possible that these hypotheses and other mechanisms by which aPL antibodies are thrombogenic be investigated. Future studies will also include the effects of different levels of antibodies, as well as effects of affinity purified and monoclonal aPL antibodies on thrombus formation.
Pierangeli
S S
SS
Department of Medicine, University of Louisville, KY 40292.
Harris
E N
EN
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000209:etiology; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology; D051379:Mice; D013927:Thrombosis / Q000209:etiology*
D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M