Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
Respiratory Cell Biology, Lund University, Lund, Sweden.
J Immunol Res. 2023 Jan 31;2023:9393497. doi: 10.1155/2023/9393497. eCollection 2023.
Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs.
Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells.
Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells.
We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.
哮喘是一种慢性炎症性疾病，肺部的结构变化定义为气道重塑。肥大细胞反应在哮喘中很重要，因为它们在激活后释放介质，诱导支气管收缩、炎症细胞募集，并且经常重塑气道。由于豚鼠表现出类似于人类气道的解剖学、生理学和药理学特征，包括肥大细胞分布和介质释放，我们评估了两种常见过敏原，屋尘螨（HDM）和猫皮屑（CDE）提取物对豚鼠肺部组织病理学变化和胰蛋白酶阳性和糜蛋白酶阳性肥大细胞组成的影响。
豚鼠经鼻内暴露于 HDM 或 CDE 中 4、8 和 12 周，每个时间点检查气道组织学。进行苏木精和伊红、苦味酸-天狼星红和过碘酸-希夫染色以评估气道炎症、胶原沉积和产生粘液的细胞。此外，使用 Astra blue 和针对胰蛋白酶和糜蛋白酶的免疫染色来可视化肥大细胞。
重复给予 HDM 或 CDE 导致炎症细胞在近端和远端气道积聚，并增加气道平滑肌质量。HDM 暴露在所有三个时间点引起上皮下胶原沉积和粘液细胞增生，而 CDE 暴露仅在 8 和 12 周时引起这些影响。HDM 和 CDE 在 8 和 12 周的挑战后均引起肥大细胞的大量增加。这种增加主要是由于表达胰蛋白酶的肥大细胞，但不是糜蛋白酶，因此表明为粘膜肥大细胞。
我们在这里表明，暴露于 HDM 和 CDE 会在豚鼠中引发类似哮喘的组织病理学改变，包括炎症细胞浸润、气道重塑和主要粘膜肥大细胞的积累。这些结果共同鼓励使用 HDM 和 CDE 过敏原来刺激豚鼠中具有临床相关性的哮喘模型。
