Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria
Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria
复制标题
DOI：
10.1016/j.ijpara.2005.12.005
复制
发表时间：
2006-04-01
影响因子：
4
通讯作者：
Hunt, Nicholas H.
中科院分区：
文献类型：
--
作者：
Potter, Sarah;Chan-Ling, Tailoi;Hunt, Nicholas H.
Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigated the role of perform in the pathogenesis of cerebral malaria in a murine model (Plasmodium berghei ANKA (PbA) infection). C5713L/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5 p.i. and became moribund on day 6 p.i. This pathology was not seen in PbA-infected, perform-deficient (pfp -/-) mice. From days 5-6 p.i. onwards there was a significant increase in mRNA for granzyme B and CD8, but not CD4. in brain tissue from PbA-infected C5713L/6 and pfp-/- mouse brains. Perform mRNA was strongly increased in the brains of PbA-infected C57BL/6 mice on day 6 p.i. Immunohistochemistry revealed increased perform staining and elevated numbers of CD8(+) cells within the cerebral microvessels in PbA-infected C57BL/6 at days 5 and 6 p.i. compared with uninfected animals. At day 6 p.i., there were TUNEL-positive cells and activated caspase-3 positive cells of endothelial morphology in the CNS of PbA-infected C57BL/6 mice. The TUNEL-positive cells were greatly reduced in pfp-/- mice. These results suggest that CD8(+)T lymphocytes induce apoptosis of endothelial cells via a perforin-dependent process, contributing to the fatal pathogenic process in murine cerebral malaria. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
