Neutrophils accelerate macrophage-mediated digestion of apoptotic cells in vivo as well as in vitro
Neutrophils accelerate macrophage-mediated digestion of apoptotic cells in vivo as well as in vitro
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DOI：
10.4049/jimmunol.175.6.3475
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发表时间：
2005-09-15
影响因子：
4.4
通讯作者：
Kobayashi, Y
中科院分区：
文献类型：
--
作者：
Iyoda, T;Nagata, K;Kobayashi, Y
通常认为，凋亡细胞的清除不会导致炎症。与此相反，我们以前发现，注射凋亡细胞到腹腔诱导炎症趋化因子，MIP-2的表达，和中性粒细胞的浸润，和抗MIP-2抗体抑制浸润显着。因为我们以前的研究表明，全身X射线照射引起中性粒细胞浸润到胸腺沿着T细胞凋亡，我们研究了中性粒细胞在凋亡细胞清除中的作用。1戈伊X线照射后12 h，神经元浸润达到高峰。免疫组化分析显示，凋亡细胞显着消失，从10.5至12小时后，x射线照射。随着中性粒细胞从皮质的内部区域移动到外周，凋亡细胞随之消失。抗MIP-2和抗CXCR 2抗体均能显著抑制中性粒细胞浸润，且抗MIP-2抗体抑制中性粒细胞浸润可延迟凋亡细胞的消失。此外，巨噬细胞介导的消化凋亡的胸腺细胞加速在体外与中性粒细胞共培养，即使中性粒细胞从巨噬细胞分离。这些结果表明，中性粒细胞募集到胸腺后，全身X射线照射，主要由MIP-2，这样的中性粒细胞可能不会诱导炎症，而是加速完全消化凋亡细胞的巨噬细胞。
It is generally believed that the clearance of apoptotic cells does not lead to inflammation. In contrast, we previously found that injection of apoptotic cells into the peritoneal cavity induced the expression of an inflammatory chemokine, MIP-2, and infiltration of neutrophils, and that anti-MIP-2 Abs suppressed the infiltration significantly. Because our previous study showed that whole-body x-irradiation caused neutrophil infiltration into the thymus along with T cell apoptosis, we examined the role of neutrophils in apoptotic cell clearance. Neutrophil infiltration reached a peak 12 h after irradiation with 1 Gy of x-rays. Immunohistological analysis revealed that apoptotic cells disappeared dramatically from 10.5 to 12 h after x-irradiation. As neutrophils moved from an inner area of the cortex to the periphery, apoptotic cells disappeared concomitantly. Either anti-MIP-2 or anti-CXCR2 Abs suppressed neutrophil infiltration significantly, and the suppression of neutrophil infiltration by anti-MIP-2 Abs delayed the disappearance of apoptotic cells. Moreover, macrophage-mediated digestion of apoptotic thymocytes was accelerated in vitro on coculturing with neutrophils, even if neutrophils were separated from macrophages. These results suggest that neutrophils are recruited to the thymus mainly by MIP-2 after whole-body x-irradiation and that such neutrophils may not induce inflammation but rather accelerate complete digestion of apoptotic cells by macrophages.