The human cathelicidin LL-37 enhances airway mucus production in chronic obstructive pulmonary disease

Airway mucus overproduction is a distinguishing feature of chronic obstructive pulmonary disease (COPD). LL-37 is the only member of human cathelicidins family of antimicrobial peptides and plays a central role in many immune and inflammatory reactions. Increasing evidence suggests the involvement of LL-37 in the pathogenesis of COPD. Here, we investigated the effects of LL-37 on airway mucus overproduction in COPD. We observed overexpression of both LL-37 and MUC5AC mucin (a major mucin component of mucus) in airways of COPD patients and found a correlation between them. We showed in vitro that LL-37 induces MUC5AC mucin production by airway epithelial NCI-H292 cells in the absence and presence of cigarette smoke extract, with TNF-α converting enzyme (TACE)–EGFR–ERK1/2 pathway and IL-8 required for the induction. Therefore, we concluded that LL-37 enhances the mucus production in COPD airways, thus contributing to the progression of COPD.     

Bronchial epithelial cells produce IL-5: Implications for local immune responses in the airways

IL-5 is a pleiotropic cytokine that promotes eosinophil differentiation and survival. While naïve bronchial epithelial cells (BEC) produce low levels of IL-5, the role of BEC-derived IL-5 in allergic airway inflammation is unknown. We now show that BEC, isolated from mice with OVA-induced allergic airway disease (AAD), produced elevated levels of IL-5 mRNA and protein as compared to BEC from naïve mice. To determine the contribution of BEC-derived IL-5 to effector responses in the airways, IL-5 deficient bone marrow chimeric mice were generated in which IL-5 expression was restricted to stromal (e.g. BEC) or hematopoietic cells. When subjected to AAD, IL-5 produced by BECs contributed to mucous metaplasia, airway eosinophilia, and OVA-specific IgA levels. Thus, IL-5 production by BEC can impact the microenvironment of the lung, modifying pathologic and protective immune responses in the airways.     

The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage

In the mammalian gastrointestinal tract, the cell fate decisions that specify the development of multiple, diverse lineages are governed in large part by interactions of stem and early lineage progenitor cells with their microenvironment, or niche. Here, we show that the gastric parietal cell (PC) is a key cellular component of the previously undescribed niche for the gastric epithelial neck cell, the progenitor of the digestive enzyme secreting zymogenic (chief) cell (ZC). Genetic ablation of PCs led to failed patterning of the entire zymogenic lineage: progenitors showed premature expression of differentiated cell markers, and fully differentiated ZCs failed to develop. We developed a separate mouse model in which PCs localized not only to the progenitor niche, but also ectopically to the gastric unit base, which is normally occupied by terminally differentiated ZCs. Surprisingly, these mislocalized PCs did not maintain adjacent zymogenic lineage cells in the progenitor state, demonstrating that PCs, though necessary, are not sufficient to define the progenitor niche. We induced this PC mislocalization by knocking out the cytoskeleton-regulating gene Cd2ap in Mist1^−/− mice, which led to aberrant E-cadherin localization in ZCs, irregular ZC-ZC junctions, and disruption of the ZC monolayer by PCs. Thus, the characteristic histology of the gastric unit, with PCs in the middle and ZCs in the base, may depend on establishment of an ordered adherens junction network in ZCs as they migrate into the base.     

大鳞副泥鳅肠道黏液细胞及消化酶活性分布特征研究

采用阿利新兰-碘酸雪夫氏反应(AB-PAS)染色法及酶学方法研究了大鳞副泥鳅成熟个体肠道各段黏液细胞分布及消化酶活性。结果表明, 大鳞副泥鳅肠道黏液细胞分为Ⅰ、Ⅱ、Ⅲ和Ⅳ 4种类型。前肠至后肠, 黏液细胞数量逐渐减少。前肠主要分布Ⅲ和Ⅳ混合型黏液细胞, 后肠则以Ⅱ和Ⅳ型酸性黏液细胞为主。肠道胰蛋白酶活性显著高于淀粉酶和脂肪酶。且后肠消化酶活性显著低于前肠和中肠。根据黏液细胞及消化酶活性分布特点, 表明大鳞副泥鳅属于杂食性鱼类, 前肠为其主要的消化吸收场所, 后肠中性黏液细胞的数量较少以及消化酶活性较低, 表明其对食物的消化吸收功能较弱, 与其为辅助呼吸功能的特点相关。     

Microridges of oral mucosal epithelium in carp,Cyprinus carpio

Summary The surface of carp oral mucosa is characterized by various patterns of microridges about 0.3 m wide, 0.1 m high, and of various lengths. To elucidate the derivation and function of these microridges, the oral epithelium was examined by light- and electron microscopy. Microridges were present only on the surfaces of the superficial cells. Therefore, microridges on renewed superficial cells are presumed to be formed after old superficial cells have been discarded, and the various patterns of microridges found on the cell surface appear to indicate the progress of their development. In thin sections, the outer leaflet of the plasma membranes of microridges stained strongly with ruthenium red, and the underlying cytoplasm was packed with many fine filaments. The superficial cells contained many secretory vesicles that were PAS-positive but Alcian blue-negative at pH 2.5 and pH 1.0. However, after sulfation the vesicles gave a positive reaction with toluidine blue. These vesicles are secreted by exocytosis at the free surface of the cells. After release, the membranes of the vesicles are thought to be utilized for formation of microridges. On the basis of these observations, the possible function of microridges is discussed.This study was supported by grants from the Ministry of Education, Science and Culture, Japan     

Early weaning accelerates the differentiation of mucous neck cells in rat gastric mucosa: Possible role of TGFα/EGFR

The development of the gastric mucosa is controlled by hormones, growth factors and feeding behavior. Early weaning (EW), which means the abrupt interruption of suckling, increases proliferation and differentiation in the rat gastric epithelium. Transforming growth factor α (TGFα) is secreted in the stomach, binds to the epidermal growth factor receptor (EGFR) and may control cell proliferation, differentiation and migration. Here, we investigated the influence of suckling–weaning transition on the differentiation of mucous neck cells in the stomach and its association to the expression of TGFα and EGFR. Fifteen-day-old Wistar rats were divided into two groups: suckling (control), in which pups were kept with the dam, and early weaning (EW), in which rats were separated from their mother and fed with hydrated powdered chow. TGFα and EGFR levels were increased at 18 days in EW animals compared to control ones (p<0.05). Histochemical reactions with Periodic Acid-Schiff reagent+Alcian Blue or Bandeiraea simplicifolia II lectin were used to stain the mucous neck cells and showed an increase in this cell population throughout EW, which was more pronounced at 17 days when compared to suckling pups (p<0.05). These morphological results were confirmed by RT-PCR for mucin 6. The levels of mucin 6 mRNA were higher in EW animals from the 16th to the 18th day (1–3 days post-weaning) when compared to the respective control group. Inhibition of EGFR through AG1478 administration to EW animals prevented the expansion of mucous neck cell population induced by EW (p<0.05). Therefore, early weaning up regulated TGFα/EGFR expression and induced differentiation of mucous neck cells. Moreover, we showed that EGFR takes part in the maturation of this cell population. We conclude that regular suckling–weaning transition is crucial to guarantee the development of the gastric mucosa.     

中华蟾蜍与黑斑蛙消化道黏液细胞的观察

目的：探索两栖类动物消化道黏液细胞的类型与分布规律。方法：利用阿利新蓝与过碘酸雪夫试剂染色法对中华蟾蜍（Bufo bufo gargazizans）、黑斑蛙（Rana nigromaculata）消化道黏液细胞进行石蜡切片和染色。结果与结论：黏液细胞表现为4个类型：Ⅰ型玫瑰红色;Ⅱ型蓝绿色;Ⅲ型紫红色;Ⅳ型蓝紫色。两种动物食管黏膜上皮中黏液细胞主要是杯状细胞,其中中华蟾蜍的黏液细胞主要为Ⅱ型和Ⅳ型细胞,黑斑蛙的黏液细胞主要Ⅲ型细胞。胃体柱状黏膜上皮细胞与胃腺颈细胞主要为Ⅰ型和Ⅲ型细胞,黏原颗粒主要集中在细胞的核上区。胃腺浅部有成团分布并着色较浅的黏液细胞,其中黑斑蛙胃腺黏液细胞主要为Ⅰ型和Ⅲ型细胞,中华蟾蜍胃腺黏液细胞主要为Ⅲ型和Ⅳ型细胞。小肠杯状细胞主要为Ⅲ型和Ⅳ型细胞。大肠杯状细胞主要为Ⅱ型和Ⅳ型细胞。     

瘤背石磺产卵前后生殖系统的组织学变化

瘤背石磺(Onchidium struma)是雌雄同体、异体交配的腹足纲贝类,其生殖系统较为复杂,通过解剖学和组织切片技术对成体瘤背石磺的生殖系统及产卵前后的组织学变化进行了系统的研究.结果表明:(1)雄性生殖系统主要南阴茎囊、阴茎、雄性附性腺、两性腺(早期主要产生精于)和储精囊等部分组成,而雌性生殖系统则由两性腺(后期主要产生卵子)、生殖细胞输送管、蛋白腺、黏液腺、受精囊和阴道等组成;(2)雄性生殖系统的组织学结构在产卵前后变化较小,但两性腺、卵蛋白腺和黏液腺的组织学在产卵前后变化显著;(3)产卵后的两性腺由于成熟卵子的排放,整体结构松散,部分腺泡中有少量未排出的成熟卵细胞和卵黄合成早期的卵母细胞;(4)产卵前的卵蛋白腺中含有许多强嗜碱性的小颗粒(组织学结构类似于卵鞘中的胚胎外周蛋白),产卵后腺体中的颗粒相对较大,且呈嗜酸性;(5)产卵前的黏液腺中存在嗜碱性区、嗜酸性区和混杂区三种区域,但是产卵前黏液腺以嗜酸性细胞为主,而产卵后的黏液腺中以嗜碱性细胞区域为主,且分泌管道中有一些嗜碱性物质.由此可见,卵蛋白腺的主要功能是分泌卵蛋白包裹受精卵形成卵外周蛋白层,而黏液腺则在产卵过程中分泌黏液物质形成卵鞘结构及链状的卵带.     

CEA、CA125、CA-50、β2-MG对腮腺粘液表皮样癌的诊断价值分析

目的:探讨CEA、CA125、CA-50、β_2-MG对腮腺粘液表皮样癌的诊断价值。方法:选择2015年6月至2017年5月本院收治的腮腺粘液表皮样癌患者30例为恶性肿瘤组及同期收治的良性腮腺肿瘤患者30例为良性肿瘤组,并选择30例健康体检者为健康对照组。采用酶促化学发光免疫分析法检测各组血清、混合唾液、健侧/患侧腮腺液中CEA、CA125含量;放射免疫分析法检测血清、混合唾液、健侧/患侧腮腺液中CA-50、β_2-MG水平。比较各组腮腺液、唾液、血清中CEA、CA125、CA-50、β_2-MG水平;分别对健侧及患侧腮腺液、混合唾液、血清中的CA-50、β_2-MG水平与CEA、CA125水平进行相关性分析。结果:肿瘤组腮腺液、唾液、血清CEA水平均明显高于健康对照组(P0.05),恶性肿瘤组患侧腮腺液、血清CEA水平明显高于良性肿瘤组(P0.05)。肿瘤组患侧腮腺液、混合唾液中CA125水平明显高于健康对照组,且恶性肿瘤组明显高于良性肿瘤组(P0.01)。肿瘤组各检测标本中CA-50水平均明显高于健康对照组(β_2-MG水平均明显低于健康对照组),恶性肿瘤组高于良性肿瘤组(P0.01)。健侧腮腺液及血清中CA-50水平与CEA水平呈显著正相关,β_2-MG水平与CEA水平呈显著负相关(P0.05)。患侧腮腺液及混合唾液中CA-50水平与CEA、CA125水平呈显著正相关,β_2-MG水平与CEA、CA125水平呈显著负相关(P0.05)。结论:患侧腮腺液、混合唾液中CEA、CA125、CA-50、β_2-MG水平检测对腮腺粘液表皮样癌的诊断有较高的参考价值。