Zhang Ya Na, Song Jia, Zhai Guan Ting, Wang Hai, Luo Ren Zhong, Li Jing Xian, Liao Bo, Ma Jin, Wang Heng, Lu Xiang, Liu Da Bo, Liu Zheng
Department of Otolaryngology-Head and Neck Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China.
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Allergy Asthma Immunol Res. 2020 Mar;12(2):274-291. doi: 10.4168/aair.2020.12.2.274.
Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps.
Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting.
The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA.
Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.
浆细胞和免疫球蛋白（Igs）在鼻息肉慢性炎症的诱导和维持中起关键作用。在二次免疫反应期间，浆细胞的存活和Ig产生受局部环境调节。本研究的目的是调查人鼻息肉中长寿浆细胞（LLPCs）的存在情况以及LLPCs的特定存活微环境。
鼻黏膜样本采用气液界面系统培养，培养上清液中的Ig水平通过酶联免疫吸附测定法进行分析。通过免疫组织化学和免疫荧光确定鼻息肉中LLPCs的特征。通过定量实时聚合酶链反应、免疫组织化学、免疫荧光和蛋白质印迹法检测神经营养因子及其受体的表达。
与正常组织相比，嗜酸性和非嗜酸性鼻息肉中CD138⁺总浆细胞和BCL2⁺浆细胞的数量均增加。即使在鼻息肉培养32天后，培养上清液中仍检测到IgG、IgA和IgE的产生。虽然培养后鼻息肉中浆细胞的总数减少，但BCL2⁺浆细胞的数量保持稳定。嗜酸性和非嗜酸性鼻息肉中神经生长因子（NGF）以及NGF的高亲和力受体原肌球蛋白受体激酶（Trk）A的表达均上调。此外，鼻黏膜组织中BCL2⁺浆细胞数量与NGF和TrkA mRNA表达呈正相关。息肉浆细胞表达TrkA。
人鼻息肉中存在一群LLPCs，NGF可能参与其长期存活。LLPCs可能是抑制鼻息肉局部Ig产生的新治疗靶点。
