Matsui Makoto, Nagakubo Daisuke, Satooka Hiroki, Hirata Takako
Department of Fundamental Biosciences, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
Biochem Biophys Res Commun. 2020 Jun 4;526(3):599-606. doi: 10.1016/j.bbrc.2020.03.122. Epub 2020 Apr 1.
Neutrophils are important phagocytic cells for host defense against pathogens. They are rapidly recruited to the site of infection, release antimicrobial peptides and cytokines, and engulf and kill microbes. Neutrophils also accumulate in allergic inflammatory sites. Here we characterized neutrophil accumulation in the nasal mucosa using a mouse model of allergic rhinitis, in which mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and then challenged by intranasal administration of OVA or PBS. In the nasal mucosa of both PBS- and OVA-challenged mice, we found a cell subset expressing the eosinophil marker Siglec-F in the Ly-6G neutrophil population. Morphological analysis of the sorted Ly-6GSiglec-F cells revealed that they were devoid of eosinophilic granules in the cytosol and were apparently neutrophils, but compared to conventional Ly-6GSiglec-F neutrophils, they had a more lobulated, "botryoid" nucleus. Siglec-F neutrophils were barely found in the nasopharynx-associated lymphoid tissue, cervical lymph nodes, the spleen, or blood. Both Siglec-F neutrophils and conventional neutrophils showed increased numbers in the nasal mucosa of OVA-challenged mice. Compared to conventional Siglec-F neutrophils, Siglec-F neutrophils exhibited an activated phenotype and enhanced effector functions. Taken together, our findings identify Siglec-F neutrophils as a novel neutrophil subset with an activated phenotype that resides specifically in the nasal mucosa.
中性粒细胞是宿主抵御病原体的重要吞噬细胞。它们能迅速募集到感染部位，释放抗菌肽和细胞因子，并吞噬和杀死微生物。中性粒细胞也会在过敏性炎症部位积聚。在此，我们使用变应性鼻炎小鼠模型对鼻黏膜中的中性粒细胞积聚进行了表征，在该模型中，小鼠通过腹腔注射卵清蛋白（OVA）进行致敏，然后通过鼻内给予OVA或磷酸盐缓冲盐水（PBS）进行激发。在PBS激发组和OVA激发组小鼠的鼻黏膜中，我们在Ly-6G阳性的中性粒细胞群体中发现了一个表达嗜酸性粒细胞标志物唾液酸结合免疫球蛋白样凝集素F（Siglec-F）的细胞亚群。对分选得到的Ly-6G阳性Siglec-F细胞进行形态学分析显示，它们的胞质中没有嗜酸性粒细胞颗粒，显然是中性粒细胞，但与传统的Ly-6G阳性Siglec-F中性粒细胞相比，它们的细胞核分叶更多，呈“葡萄状”。在鼻咽相关淋巴组织、颈部淋巴结、脾脏或血液中几乎未发现Siglec-F中性粒细胞。在OVA激发组小鼠的鼻黏膜中，Siglec-F中性粒细胞和传统中性粒细胞的数量均增加。与传统的Siglec-F中性粒细胞相比，Siglec-F中性粒细胞表现出活化的表型和增强的效应功能。综上所述，我们的研究结果确定Siglec-F中性粒细胞是一种具有活化表型的新型中性粒细胞亚群，特异性地存在于鼻黏膜中。
