Anti-DNA antibodies cross-reactive with β2-glycoprotein I induce monocyte tissue factor through the TLR9 pathway
| Autor: | Yumi Makino, Tetsuo Kubota, Osamu Hoshi, Masumi Saito, Kumi Inoue, Yoshino Watanabe |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
toll-like receptor 9
biology β2-glycoprotein i Monocyte Immunology Cell anti-dna antibodies TLR9 RC581-607 tissue factor Endocytosis Molecular biology chemistry.chemical_compound Tissue factor medicine.anatomical_structure systemic lupus erythematosus chemistry Cardiolipin medicine biology.protein Immunology and Allergy Immunologic diseases. Allergy Antibody antiphospholipid syndrome DNA |
| Zdroj: | Immunological Medicine, Vol 44, Iss 2, Pp 124-135 (2021) |
| ISSN: | 2578-5826 |
| DOI: | 10.1080/25785826.2020.1796285 |
| Popis: | Antibodies specific for cardiolipin (CL)-β2-glycoprotein I (β2GPI) are known to induce tissue factor (TF) expression by monocytes and endothelial cells which leads to a prothrombotic state in antiphospholipid syndrome (APS), but the mechanism is not fully elucidated. Previously, we reported that the mouse monoclonal anti-CL-β2GPI antibody WB-6 cross-reacts with DNA, enters monocytes via binding to cell surface DNA, and induces TF expression. The current study aimed to identify the intracellular signaling pathways involved in this process. The binding of WB-6 to CL-β2GPI or DNA, and endocytosis was not prevented by chloroquine, but pre-treatment of the cells with chloroquine significantly suppressed TF expression. TLR9 inhibitory oligodeoxynucleotide also suppressed the WB-6-induced TF expression, suggesting a pivotal role of the TLR9 pathway in TF production. Serum antibodies obtained from a patient with APS accompanying systemic lupus erythematosus (SLE) bound to both CL-β2GPI and DNA, and induced TF in normal monocytes. This effect was suppressed by chloroquine, and abolished by removal of the DNA-binding activity. These results suggest that induction of TF expression results from TLR9 activation by DNA which was internalized together with cross-reactive antibodies produced in secondary APS accompanying SLE. |
| Databáze: | OpenAIRE |
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