The influence on the immunomodulatory effects of dying and dead cells of Annexin V
| Autor: | Ahmed Sheriff, Friederike Pausch, Bent Brachvogel, Udo S. Gaipl, Luis E. Muñoz, Ernst Pöschl, Sandra Franz, Dorothee von Laer, Peter Kern, Christian Stach, Birgit Vogt, Martin Herrmann, Wolfgang Baum, Barbara G. Fürnrohr |
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| Rok vydání: | 2006 |
| Předmět: |
Necrosis
Immunology Anti-Inflammatory Agents Apoptosis Phosphatidylserines Biology Mice chemistry.chemical_compound Immune system Phagocytosis Annexin medicine Animals Humans Immunologic Factors Immunology and Allergy Macrophage Secretion Annexin A5 Cells Cultured Inflammation Immunity Cellular Mice Inbred BALB C Macrophages Models Immunological Cell Biology Phosphatidylserine In vitro Cell biology chemistry HIV-1 Cytokines Female Immunization medicine.symptom |
| Zdroj: | Journal of Leukocyte Biology. 81:6-14 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0306166 |
| Popis: | Apoptotic and necrotic cells expose phosphatidylserine (PS). This membrane modification ensures a swift recognition and uptake by phagocytes of the dying and dead cells. Annexin V (AxV) preferentially binds to anionic phospholipids and thereby, modulates the clearance process. First, we analyzed the influence of AxV on the immunogenicity of apoptotic cells. The addition to apoptotic cells of AxV prior to their injection into mice increased their immunogenicity significantly. Next, we studied the influence of endogenous AxV on the allogeneic reaction against apoptotic and necrotic cells. To preserve heat-labile, short-lived “danger signals,” we induced necrosis by mechanical stress. Wild-type mice showed a strong, allogeneic delayed-type hypersensitivity (DTH) reaction. In contrast, AxV-deficient animals showed almost no allogeneic DTH reaction, indicating that endogenous AxV increases the immune response against dead cells. Furthermore, AxV-deficient macrophages had a higher immunosuppressive potential in vitro. Next, we analyzed the influence of AxV on chronic macrophage infection with HIV-1, known to expose PS on its surface. The infectivity in human macrophages of HIV-1 was reduced significantly in the presence of AxV. Finally, we show that AxV also blocked the in vitro uptake by macrophages of primary necrotic cells. Similar to apoptotic cells, necrotic cells generated by heat treatment displayed an anti-inflammatory activity. In contrast, mechanical stress-induced necrotic cells led to a decreased secretion of IL-10, indicating a more inflammatory potent-ial. From the experiments presented above, we conclude that AxV influences the clearance of several PS-exposing particles such as viruses, dying, and dead cells. |
| Databáze: | OpenAIRE |
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