Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha
Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha
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DOI：
10.1038/381077a0
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发表时间：
1996-05-02
期刊：
影响因子：
64.8
通讯作者：
Abraham, SN
中科院分区：
文献类型：
--
作者：
Malaviya, R;Ikeda, T;Abraham, SN
尽管肥大细胞与包括速发型超敏反应和间质性膀胱炎在内的多种炎症性疾病有关（1，2），但其在体内的生理作用尚不清楚。我们使用充分表征的肥大细胞缺陷小鼠模型研究了肥大细胞在宿主防御细菌感染中的作用（3，4）。我们在这里报告，肥大细胞，这是选择性地位于门户网站的细菌进入，是重要的宿主防御。肥大细胞缺陷型WBB 6 F1-W/W-v小鼠（W/W-v）清除肠杆菌的效率比WBB 6 F1 +/+（+/+）小鼠或肥大细胞重建的W/W-v（W/W-v + MC）小鼠低20倍。随着细菌接种量的增加，只有W/W-v小鼠死亡（80%）。W/W-v小鼠中有限的细菌清除与受损的中性粒细胞流入直接相关。肥大细胞趋化因子TNF-α与中性粒细胞反应有关，因为TNF-α仅在+/+和W/W-v + MC小鼠中局部释放，TNF-α特异性抗体阻断了70%以上的中性粒细胞流入，纯化的肥大细胞在与细菌孵育后释放TNF-α。此外，1型菌毛亚基FimH是肥大细胞活化和中性粒细胞流入所必需的肠杆菌组分，因为与野生型细菌相比，同基因FimH（-）突变体在+/+小鼠中引起有限的中性粒细胞反应。
ALTHOUGH mast cells have been implicated in a variety of inflammatory conditions including immediate hypersensitivity and interstitial cystitis,(1,2) their physiological role in the body is unknown. We investigated the role of mast cells in host defence against bacterial infections using a well characterized mast-cell-deficiency mouse model(3,4). We report here that mast cells, which are selectively located at portals of bacterial entry, are important to host defence. Mast-cell-deficient WBB6F1-W/W-v mice (W/W-v) were up to 20-fold less efficient in clearing enterobacteria than WBB6F1+/+ (+/+)mice or mast-cell-reconstituted W/W-v (W/W-v + MC) mice. With higher bacterial inocula, only W/W-v mice died (80%). The limited bacterial clearance in W/W-v mice directly correlated with impaired neutrophil influx. The mast-cell chemoattractant TNF-alpha was implicated in the neutrophil response because TNF-alpha was locally released only in +/+ and W/W-v + MC mice, TNF-alpha-specific antibodies blocked over 70% of the neutrophil influx, and purified mast cells released TNF-alpha upon incubation with bacteria. Additionally, the type-1 fimbrial subunit, FimH, was the necessary enterobacterial component for mast-cell activation and neutrophil influx because an isogenic FimH(-) mutant evoked a limited neutrophil response in +/+ mice compared to wild-type bacteria.