(NZW x BXSB)F1 mouse. A new animal model of idiopathic thrombocytopenic purpura.

Abstract

There has recently been an increase in data indicating that autoimmune mechanisms are involved in the etiopathogenesis of idiopathic thrombocytopenic purpura (ITP) (1, 2). Although antibodies that react with platelets are found in most patients with ITP, the pathogenetic nature of the antibodies remains to be clarified . The discovery of an animal model for ITP has therefore been long-awaited. Here we have found that (NZW x BXSB)Fi (W/B Fi) mice, which develop lupus nephritis with myocardial infarction (3), show thrombocytopenia with age, and that this is due to the presence ofboth platelet-associated antibodies (PAA) and circulating antiplatelet antibodies.Recently, we have demonstrated that allogeneic bone marrow transplantation (ABMT) has curative effects on autoimmune diseases in (NZB x NZW)FI, BXSB, MRL/MP-lpr/lpr (MRL/lpr), and NOD mice (4-6) . These results prompted us to examine whether ABMT can be used to treat ITP. In the present study, we provide evidence that the transplantation of bone marrow from BALB/c mice to W/B F, mice does indeed have preventative and curative effects on ITP Materials and MethodsMice.Mice ofthe inbred strain BALB/c nu/nu, BALB/c, C57B/6, C3H/HeN, BXSB, NZW were raised under specific pathogen-free conditions in our animal facility. W/B F, males were obtained from the Nippon Shinyaku Research Laboratories, Kyoto, Japan.Staining Procedure andData Analysis.Platelet-rich plasma was obtained as described previously (7) . The platelets were suspended in 1% paraformaldehyde solution for 5 min. After

Exacerbation of autoantibody-mediated thrombocytopenic purpura by infection with mouse viruses

“…4 (NZW ϫ BXSB)F1 mice spontaneously produce antiplatelet autoantibodies, leading to thrombocytopenia in the context of a complex autoimmune syndrome dissimilar to organspecific ITP. 5 Production of antiplatelet autoantibodies through molecular mimicry may be studied by immunizing mice with rat platelets, but the resulting thrombocytopenia is at best moderate and very transient in normal mice. 6 Here, we report on the effect of infection with the common mouse viruses lactate dehydrogenaseelevating virus (LDV) and mouse hepatitis virus (MHV), on platelet counts in mice with preexisting antiplatelet autoantibodies.…”

IgG inhibits the increase of platelet-associated C3 stimulated by anti-platelet antibodies

“…Idiopalhic thrombocylopenic purpuni (ITP) is a .syndrome which is caused by circulating antibodies that react with the platelet membrane [1.2], It is thought that platelet-associated IgG (PAlgG) has an important role in the mechanism of ITP, because an incrca.se in PAIgG is closely correlated with a deerease in the platelet count in this disease [1][2][3][4][5], Furthermore, high levels of PAIgM and platelet-associated complement component 3 (PAC3) are also considered to be of pathogenetic relevance to thrombocytopenia in ITP [2.6-9].…”

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets

“…It has been reported that autoimmune diseases can be treated by BMT without immunosuppressants in animal models. 3,[29][30][31][32][33] Even in humans, the effects of BMT have also been reported. [34][35][36] Therefore, the simultaneous transplantation of BMCs plus PIs is an ideal therapy for T1DM, as the rejection of grafted PIs and autoimmune reaction to PIs can be prevented if BMT can be easily performed without the long-term usage of immunosuppressants.…”