Histamine acts via H4-receptor stimulation to cause augmented inflammation when lipopolysaccharide is co-administered with a nitrogen-containing bisphosphonate
Histamine acts via H4-receptor stimulation to cause augmented inflammation when lipopolysaccharide is co-administered with a nitrogen-containing bisphosphonate
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当脂多糖与含氮二膦酸盐共同给药时，组胺通过 H4 受体刺激起作用，引起炎症加剧
DOI：
10.1007/s00011-022-01650-7
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发表时间：
2022
影响因子：
6.7
通讯作者：
Endo Yasuo
中科院分区：
文献类型：
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作者：
Bando Kanan;Tanaka Yukinori;Takahashi Tetsu;Sugawara Shunji;Mizoguchi Itaru;Endo Yasuo
目的和方法含氮双膦酸盐(NBPS，抗骨吸收药)有炎症副作用。阿伦磷酸钠(Ale，一种NBP)与细菌细胞壁成分LPS(细菌细胞壁成分)一起皮内注射小鼠耳廓，可引起依赖IL-1和中性粒细胞的耳肿胀。结果ALE通过诱导组氨酸脱羧酶(HDC)增加耳廓内组胺的含量，从而使耳廓内的组胺含量增加。这种诱导作用可被内毒素增强。在HDC缺陷的小鼠中，没有诱导出这种扩大的耳朵肿胀。在峰值肿胀时，74.5%的HDC表达细胞为中性粒细胞，仅0.2%为肥大细胞(MC)。组胺H4受体(H4R)拮抗剂可显著降低肿胀，但H1R拮抗剂不能。在MC缺乏的小鼠中，出人意料的是，Ale + 脂多糖导致了比正常小鼠更长时间的耳肿胀，这种肿胀更明显、更持久。巨噬细胞高表达H4Rs，并在H4R激动剂作用下产生炎性细胞因子MCP-1和抗炎细胞因子IL-10。结论HDC诱导产生的组胺主要存在于中性粒细胞中，刺激H4Rs，导致MCs产生单核细胞趋化蛋白-1(MCP-1)，从而增强Ale + 诱导的耳肿胀。由于MCP-1也是由其他细胞产生的，MCs及其H4R对扩大耳肿胀的贡献是部分的。在肿胀的后期，MC可能通过产生IL-10发挥抗炎作用。
Objective and methodsNitrogen-containing bisphosphonates (NBPs, anti-bone-resorptive agents) have inflammatory side-effects. Alendronate (Ale, an NBP) intradermally injected into mouse ear-pinnae together with LPS (bacterial cell-wall component) induces augmented ear-swelling that depends on IL-1 and neutrophils. Using this model, we examined histamine’s involvement in Ale + LPS-induced inflammation.ResultsAle increased histamine in ear-pinnae by inducing histidine decarboxylase (HDC). This induction was augmented by LPS. In HDC-deficient mice, such augmented ear-swelling was not induced. At peak-swelling, 74.5% of HDC-expressing cells were neutrophils and only 0.2% were mast cells (MCs). The augmented swelling was markedly reduced by a histamine H4-receptor (H4R) antagonist, but not by an H1R antagonist. In MC-deficient mice, unexpectedly, Ale + LPS induced prolonged ear-swelling that was augmented and more persistent than in normal mice. MCs highly expressed H4Rs and produced MCP-1(inflammatory cytokine that recruits macrophages) and IL-10 (anti-inflammatory cytokine) in response to an H4R agonist.ConclusionHistamine produced by HDC-induction mainly in infiltrated neutrophils stimulates H4Rs, leading to augmented Ale + LPS-induced ear-swelling via MCP-1 production by MCs. Since MCP-1 is produced by other cells, too, the contribution of MCs and their H4Rs to augmented ear-swelling is partial. In the later phase of the swelling, MCs may be anti-inflammatory via IL-10 production.
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影响因子：
4.6
作者：
Jun Takai;H. Ohtsu;Atsushi Sato;S. Uemura;T. Fujimura;Masayuki Yamamoto;Takashi Moriguchi
通讯作者：
Jun Takai;H. Ohtsu;Atsushi Sato;S. Uemura;T. Fujimura;Masayuki Yamamoto;Takashi Moriguchi
影响因子：
4.8
作者：
Alcaniz, Lorena;Vega, Antonio;Monteseirin, Javier
通讯作者：
Monteseirin, Javier
氨基烷基双膦酸盐是骨吸收的有效抑制剂，可诱导组胺合成的长期刺激并增加体内巨噬细胞、粒细胞和破骨细胞的数量
影响因子：
4.2
作者：
Y. Endo;Masanori Nakamura;T. Kikuchi;H. Shinoda;Y. Takeda;Y. Nitta;K. Kumagai
通讯作者：
K. Kumagai
Yasuo Endo：“通过重组白细胞介素 1 和肿瘤坏死因子诱导小鼠组织中的组氨酸和鸟氨酸脱羧酶活性”Biochem。
DOI：
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发表时间：
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期刊：
影响因子：
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作者：
通讯作者：
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影响因子：
6.4
作者：
Shiraishi, M;Hirasawa, N;Ohuchi, K
通讯作者：
Ohuchi, K