Adoptive transfer of mast cells abolishes the inflammatory refractoriness to allergen in diabetic rats

Adoptive transfer of mast cells abolishes the inflammatory refractoriness to allergen in diabetic rats
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DOI:
10.1159/000071489
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发表时间:
2003-07-01
影响因子:
2.8
通讯作者:
Sílva, PMRE
Sílva, PMRE
中科院分区:
医学3区
文献类型:
--
作者:
Barreto, ED;Carvalho, VD;Sílva, PMRE

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肥大细胞是关键的分泌细胞,主要参与过敏原引起的炎症反应,在实验性化学性糖尿病后表达下调。在这里,我们测试了肥大细胞数量和反应性的减少将解释糖尿病大鼠对过敏原诱导的炎症反应不足的假设。我们发现,静脉注射四氧嘧啶可明显减少糖尿病大鼠致敏回肠、气管和皮肤组织中组胺的过敏性释放。同样,主动和被动致敏的糖尿病大鼠与致敏的非糖尿病大鼠相比,胸膜肥大细胞脱颗粒和蛋白外渗的过敏原诱导较弱,这与胸腔中肥大细胞数量的显著减少平行。糖尿病大鼠肠系膜中的肥大细胞数量也明显减少。通过移植致敏的非糖尿病大鼠的肥大细胞,糖尿病大鼠变应原诱发的血浆渗漏被修复。此外,过继地将糖尿病患者的致敏肥大细胞转移到幼稚动物身上,与转移致敏幼稚肥大细胞后的反应相比,导致了较低的过敏原诱导渗出量。组胺释放实验证明,纯化的糖尿病大鼠肥大细胞在体外对抗原和化合物48/80刺激反应低下。因此,我们的结果表明,糖尿病动物对变应原攻击不耐受的现象似乎是由于肥大细胞数量和反应性的减少所致。版权所有(C)2003 S.Karger AG,巴塞尔。
Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells. Copyright (C) 2003 S. Karger AG, Basel.