Zhang Shouting, Witasp Erika, Lauwen Marjolein, Fadeel Bengt
Cell Death Research Group, Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
FEBS Lett. 2008 Oct 15;582(23-24):3501-8. doi: 10.1016/j.febslet.2008.09.020. Epub 2008 Sep 18.
Macrophage clearance of dying cells is of crucial importance to maintain tissue homeostasis. Here, we show that brief treatment (15min) of Jurkat T cells with agonistic anti-Fas antibodies or recombinant Fas ligand results in efficient phagocytosis by human monocyte-derived macrophages prior to the occurrence of common biomarkers of apoptosis. Similar findings were obtained when using primary human T cells. Macrophage engulfment of pre-apoptotic target cells was suppressed in the absence of serum. Moreover, pre-apoptotic cells secreted annexin I and administration of Boc1, a formyl peptide receptor/lipoxin receptor antagonist markedly attenuated their engulfment. Finally, pre-apoptotic Jurkat cells induced lower macrophage production of tumor necrosis factor-alpha and higher production of interleukin-10 in comparison to apoptotic target cells.
巨噬细胞清除垂死细胞对于维持组织稳态至关重要。在此，我们表明，用激动性抗Fas抗体或重组Fas配体对Jurkat T细胞进行短暂处理（15分钟），会在凋亡常见生物标志物出现之前，导致人单核细胞衍生的巨噬细胞进行高效吞噬作用。使用原代人T细胞时也获得了类似的结果。在无血清的情况下，巨噬细胞对凋亡前靶细胞的吞噬作用受到抑制。此外，凋亡前细胞分泌膜联蛋白I，并且给予甲酰肽受体/脂氧素受体拮抗剂Boc1可显著减弱它们的吞噬作用。最后，与凋亡靶细胞相比，凋亡前的Jurkat细胞诱导巨噬细胞产生的肿瘤坏死因子-α较低，而白细胞介素-10的产生较高。
