The influence on the immunomodulatory effects of dying and dead cells of Annexin V

The influence on the immunomodulatory effects of dying and dead cells of Annexin V,10.1189/jlb.0306166,Journal of Leukocyte Biology,Luis E. Munoz,Sand

The influence on the immunomodulatory effects of dying and dead cells of Annexin V   (Citations: 12)
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Luis E. Munoz, Sandra Franz, Friederike Pausch, Barbara Furnrohr, Ahmed Sheriff, Birgit Vogt, Peter M. Kern, Wolfgang Baum, Christian Stach, Dorothee von Laer, Bent Brachvogel, Ernst Poschl
Apoptotic and necrotic cells expose phosphatidylserine (PS). This membrane modifi- cation ensures a swift recognition and uptake by phagocytes of the dying and dead cells. Annexin V (AxV) preferentially binds to anionic phospho- lipids and thereby, modulates the clearance pro- cess. First, we analyzed the influence of AxV on the immunogenicity of apoptotic cells. The addi- tion to apoptotic cells of AxV prior to their in- jection 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 in- duced necrosis by mechanical stress. Wild-type mice showed a strong, allogeneic delayed-type hypersensitivity (DTH) reaction. In contrast, AxV-deficient animals showed almost no alloge- neic 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 infectiv- ity 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. J. Leukoc. Biol. 81: 6-14; 2007.
Journal: Journal of Leukocyte Biology - J LEUKOCYTE BIOL , vol. 81, no. 1, pp. 6-14, 2006
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