Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice
Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice
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DOI：
10.1111/exd.12985
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Endo, Yasuo
中科院分区：
文献类型：
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作者：
Kinbara, Masayuki;Bando, Kanan;Endo, Yasuo
我们以前曾报道，镍（Ni）过敏反应是最小的小鼠缺乏组胺形成酶组氨酸脱羧酶（HDC-KO），这表明在镍过敏反应的组胺的参与。然而，目前尚不清楚组胺是如何参与镍过敏的过程。在这里，我们研究了组胺在镍过敏的作用，使用我们以前建立的小鼠模型。通过腹腔注射NiCl 2-脂多糖（LPS）混合物使小鼠对Ni致敏。10天后，过敏性炎症引起的挑战耳廓与氯化镍皮内。然后，测量耳肿胀。在致敏或激发前1 h静脉注射吡拉明（组胺H1受体拮抗剂）或色甘酸盐（肥大细胞稳定剂）。在细胞转移实验中，将来自Ni致敏供体小鼠的脾细胞静脉内转移到非致敏受体小鼠中。在致敏和非致敏小鼠中，1 mM或更多的NiCl 2（注射到耳廓）诱导一过性非过敏性炎症（Ni-TI）伴随肥大细胞脱粒。LPS不影响此Ni-TI的大小。当在Ni-TI之前给药（在致敏或激发步骤）时，吡拉明和色甘酸盐可降低Ni-TI或随后的过敏性炎症，但如果在Ni-TI消退时给药，则不会。HDC-KO和H1受体KO小鼠的实验，以及使用这些小鼠的细胞转移实验，证明了组胺参与致敏和激发步骤。这些结果表明，肥大细胞组胺介导的镍-TI促进随后的过敏性炎症反应镍，提高的可能性，控制镍-TI的药物可能是有效的预防或减少镍过敏。
We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase (HDC-KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2-lipopolysaccharide (LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2. Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 mM or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni-TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni-TI. Pyrilamine and cromoglicate reduced either the Ni-TI or the ensuing allergic inflammation when administered before Ni-TI (at either the sensitization or elicitation step), but not if administered when the Ni-TI had subsided. Experiments on HDC-KO and H1-receptor-KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni-TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni-TI by drugs may be effective at preventing or reducing Ni allergy.