Human NK cells lyse organ-specific endothelial cells: Analysis of adhesion and cytotoxic mechanisms
Human NK cells lyse organ-specific endothelial cells: Analysis of adhesion and cytotoxic mechanisms
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DOI：
10.4049/jimmunol.174.9.5573
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Chouaib, S
中科院分区：
文献类型：
--
作者：
Bielawska-Pohl, A;Crola, C;Chouaib, S
Human organ-specific microvascular endothelial cells (ECs) were established and used in the present study to investigate their susceptibility to natural killer cell line (NKL)-induced lysis. Our data indicate that although IL-2-stimulated NKL (NKL2) cells adhered to the human peripheral (HPLNEC.B3), mesenteric lymph node (HNILNEQ, brain (HBrMEC), and lung (HLMEC) and skin (HSkMEC.2) ECs, they significantly killed these cells quite differently. A more pronounced lysis of OSECs was also observed when IL-2-stimulated, purified peripheral blood NK cells were used as effector cells. In line with the correlation observed between adhesion pattern and the susceptibility to NKL2-mediated killing, we demonstrated using different chelators that the necessary adhesion step was governed by an Mg2+-dependent, but Ca2+-independent, mechanism as opposed to the subsequent Ca2+- dependent killing. To identify the cytotoxic pathway used by NKL2 cells, the involvement of the classical and alternate pathways was examined. Blocking of the Ca2+-dependent cytotoxicity pathway by EGTA/MgCl, significantly inhibited endothelial target cell killing, suggesting a predominant role for the perforin/granzyme pathway. Furthermore, using confocal microscopy, we demonstrated that the interaction between NKL2 effectors and ECs induced cytochrome c release and Bid translocation in target cells, indicating an involvement of the mitochundrial pathway in NKL2-induced EC death. In addition, although all tested cells were sensitive to the cytotoxic action of TNF, no susceptibility to TRAIL or anti-Fas mAb was observed. The present studies emphasize that human NK cell cytotoxicity toward ECs may be a potential target to block vascular injury.
