The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas' disease by reducing the platelet sialic acid contents

被引:85
作者
Tribulatti, MV
Mucci, J
Van Rooijen, N
Leguizamón, MS
Campetella, O
机构
[1] Univ Nacl San Martin, Inst Invest Biotecnol, Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Fac Med, Dept Microbiol, Buenos Aires, DF, Argentina
[3] Free Univ Amsterdam, Fac Med, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands
关键词
D O I
10.1128/IAI.73.1.201-207.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Strong thrombocytopenia is observed during acute infection with Trypanosoma cruzi, the parasitic protozoan agent of American trypanosomiasis or Chagas' disease. The parasite sheds trans-sialidase, an enzyme able to mobilize the sialyl residues on cell surfaces, which is distributed in blood and is a virulence factor. Since the sialic acid content on the platelet surface is crucial for determining the half-life of platelets in blood, we examined the possible involvement of the parasite-derived enzyme in thrombocytopenia induction. We found that a single intravenous injection of trans-sialidase into naive mice reduced the platelet count by 50%, a transient effect that lasted as long as the enzyme remained in the blood. CD43(-/-) mice were affected to a similar extent. When green fluorescent protein-expressing platelets were treated in vitro with trans-sialidase, their sialic acid content was reduced together with their life span, as determined after transfusion into naive animals. No apparent deleterious effect on the bone marrow was observed. A central role for Kupffer cells in the clearance of trans-sialidase-altered platelets was revealed after phagocyte depletion by administration of clodronate-containing liposomes and splenectomy. Consistent with this, parasite strains known to exhibit more trans-sialidase activity induced heavier thrombocytopenia. Finally, the passive transfer of a trans-sialidase-neutralizing monoclonal antibody to infected animals prevented the clearance of transfused platelets. Results reported here strongly support the hypothesis that the trans-sialidase is the virulence factor that, after depleting the sialic acid content of platelets, induces the accelerated clearance of the platelets that leads to the thrombocytopenia observed during acute Chagas' disease.
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页码:201 / 207
页数:7
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