Protective roles of mast cells and mast cell-derived TNF in murine malaria
Protective roles of mast cells and mast cell-derived TNF in murine malaria
复制标题
DOI：
10.4049/jimmunol.177.5.3294
复制
发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Watanabe, Naohiro
中科院分区：
文献类型：
--
作者：
Furuta, Takahisa;Kikuchi, Takane;Watanabe, Naohiro
TNF在疟疾的保护和发病中起重要作用。虽然肥大细胞被认为是肿瘤坏死因子的来源之一，但肥大细胞与疟疾发病机制之间的关系却知之甚少。在这项研究中，肥大细胞缺陷型WBB 6 F（1）-W/W-v（W/W-v）和对照同窝出生的WBB 6 F（1）（+/+）（+/+）小鼠感染1 × 10（5）伯氏疟原虫ANKA。与W/W-v小鼠相比，+/+小鼠具有较低的寄生虫血症和较高的TNF水平。W/W-v小鼠的抵抗力下降被认为是由于肥大细胞和TNF。用+/+小鼠或TNF-/-小鼠的骨髓源性肥大细胞（BMMC）重建的W/W-v小鼠实验证实了这一事实。与W/W-v小鼠相比，具有+/+小鼠BMMC的W/W-v小鼠表现出较低的寄生虫血症和死亡率，伴随显著较高的TNF水平。携带TNF-/-小鼠骨髓基质细胞的W/W-v小鼠的寄生虫血症高于TNF +/+小鼠。抗IgE或化合物48/80激活肥大细胞导致TNF的释放和寄生虫血症的减少。此外，与W/W-v小鼠相比，感染后在+/+小鼠和用+/+小鼠的BMMC重建的W/W-v小鼠中观察到脾脏肥大和脾脏中肥大细胞数量增加。这些发现提出了一种新的机制，肥大细胞和肥大细胞衍生的TNF在疟疾中发挥保护作用。
TNF plays important roles in the protection and onset of malaria. Although mast cells are known as a source of TNF, little is known about the relationship between mast cells and pathogenesis of malaria. In this study, mast cell-deficient WBB6F(1)-W/W-v (W/W-v) and the control littermate WBB6F(1)(+/+) (+/+) mice were infected with 1 x 10(5) of Plasmodium berghei ANKA. +/+ mice had lower parasitemia with higher TNF levels, as compared with W/W-v mice. Diminished resistance in W/W-v mice was considered to be due to mast cells and TNF. This fact was confirmed by experiments in W/W-v mice reconstituted with bone marrow-derived mast cells (BMMCs) of +/+ mice or of TNF-/- mice. W/W-v mice with BMMCs of +/+ mice exhibit lower parasitemia and mortality accompanying significantly higher TNF levels than those of W/W-v mice. Parasitemia in W/W-v mice with BMMCs of TNF-/- mice was higher than that in +/+ mice. Activation of mast cells by anti-IgE or compound 48/80 resulted in release of TNF and decrease of parasitemia. In addition, splenic hypertrophy and increased number of mast cells in the spleen were observed after infection in +/+ mice and W/W-v mice reconstituted with BMMCs of +/+ mice as compared with W/W-v mice. These findings propose a novel mechanism that mast cells and mast cell-derived TNF play protective roles in malaria.