β2-glycoprotein I, the major target in antiphospholipid syndrome, is a special human complement regulator
-
- Katharina Gropp
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Nadia Weber
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Michael Reuter
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Sven Micklisch
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Isabell Kopka
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Teresia Hallström
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
-
- Christine Skerka
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
説明
<jats:title>Abstract</jats:title><jats:p>The human plasma protein β2-glycoprotein I (β2-GPI) is the major target of autoantibodies associated with antiphospholipid syndrome. However, the biologic function of this abundant protein is still unclear. Here we identify β2-GPI as a complement regulator. β2-GPI circulates in the plasma in an inactive circular form. On surface binding, such as to apoptotic cells, β2-GPI changes conformation to an elongated form that acquires C3/C3b binding activities. β2-GPI apparently changes conformation of C3, so that the regulator factor H attaches and induces subsequent degradation by the protease factor I. β2-GPI also mediates further cleavage of C3/C3b compared with factor H alone. Our data provide important insights into innate immune regulation by plasma protein β2-GPI, which may be exploited in the prevention and therapy of autoimmune disease antiphospholipid syndrome.</jats:p>
収録刊行物
-
- Blood
-
Blood 118 (10), 2774-2783, 2011-09-08
American Society of Hematology