Lipopolysaccharide-induced expansion of histidine decarboxylase-expressing Ly6G+ myeloid cells identified by exploiting histidine decarboxylase BAC-GFP transgenic mice
Lipopolysaccharide-induced expansion of histidine decarboxylase-expressing Ly6G+ myeloid cells identified by exploiting histidine decarboxylase BAC-GFP transgenic mice
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DOI：
10.1038/s41598-019-51716-6
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发表时间：
2019-10
影响因子：
4.6
通讯作者：
Jun Takai;H. Ohtsu;Atsushi Sato;S. Uemura;T. Fujimura;Masayuki Yamamoto;Takashi Moriguchi
中科院分区：
文献类型：
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作者：
Jun Takai;H. Ohtsu;Atsushi Sato;S. Uemura;T. Fujimura;Masayuki Yamamoto;Takashi Moriguchi
组胺是一种生物胺，主要在肥大细胞和嗜碱性细胞中产生，在刺激时引起过敏反应。组氨酸脱羧酶（HDC）是一种独特的催化组胺合成的酶。因此，时空特异性的hdcgene表达谱可以代表不同病理生理条件下产生组胺的细胞的定位。尽管组胺的生物活性已被明确，但在各种疾病背景下，hdcgene表达的调控机制和产生组胺的细胞群的分布仍未被探索。为了解决这些问题，我们建立了一个组氨酸脱羧酶BAC（细菌人工染色体）dna导向的GFP报告基因转基因小鼠，使用293 kb的BAC克隆包含整个hdcgene位点和扩展的侧翼序列（hdl -GFP）。我们发现，在hdl -GFP小鼠中，GFP的表达模式忠实地再现了传统组胺产生细胞的表达模式，并且GFP的表达水平反映了脂多糖（LPS）诱导的脓毒性肺中hdc表达的增加。值得注意的是，在脓毒症期间，CD11b+Ly6G+Ly6Clowmyeloid细胞群在肺部积聚，这些细胞大多数表达高水平的GFP，并且确实含有组胺。本研究揭示了脓毒症期间产生组胺的骨髓细胞群的积累，可能参与了脓毒症的免疫过程。
Histamine is a biogenic amine that is chiefly produced in mast cells and basophils and elicits an allergic response upon stimulation. Histidine decarboxylase (HDC) is a unique enzyme that catalyzes the synthesis of histamine. Therefore, the spatiotemporally specificHdcgene expression profile could represent the localization of histamine-producing cells under various pathophysiological conditions. Although the bioactivity of histamine is well defined, the regulatory mechanism ofHdcgene expression and the distribution of histamine-producing cell populations in various disease contexts remains unexplored. To address these issues, we generated a histidine decarboxylase BAC (bacterial artificial chromosome) DNA-directed GFP reporter transgenic mouse employing a 293-kb BAC clone containing the entireHdcgene locus and extended flanking sequences (Hdc-GFP). We found that the GFP expression pattern in theHdc-GFP mice faithfully recapitulated that of conventional histamine-producing cells and that the GFP expression level mirrored the increasedHdcexpression in lipopolysaccharide (LPS)-induced septic lungs. Notably, a CD11b+Ly6G+Ly6Clowmyeloid cell population accumulated in the lung during sepsis, and most of these cells expressed high levels of GFP and indeed contain histamine. This study reveals the accumulation of a histamine-producing myeloid cell population during sepsis, which likely participates in the immune process of sepsis.