Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
College of Public Health, Medical and Veterinary Sciences, Australian Institute of Tropical Health and Medicine, Molecular Allergy Research Laboratory, James Cook University, Townsville, Queensland, Australia.
Mol Immunol. 2019 Aug;112:140-150. doi: 10.1016/j.molimm.2019.04.029. Epub 2019 May 15.
The prevalence of fish allergy among fish-processing workers is higher than in the general population, possibly due to sensitization via inhalation and higher exposure. However, the response of the bronchial epithelium to fish allergens has never been explored. Parvalbumins (PVs) from bony fish are major sensitizers in fish allergy, while cartilaginous fish and their PVs are considered less allergenic. Increasing evidence demonstrates that components other than proteins from the allergen source, such as low molecular weight components smaller than 3 kDa (LMC) from pollen, may act as adjuvants during allergic sensitization. We investigated the response of bronchial epithelial cells to PVs and to LMC from Atlantic cod, a bony fish, and gummy shark, a cartilaginous fish. Polarized monolayers of the bronchial epithelial cell line 16HBE14o- were stimulated apically with fish PVs and/-or the corresponding fish LMC. Barrier integrity, transport of PVs across the monolayers and release of mediators were monitored. Intact PVs from both the bony and the cartilaginous fish were rapidly internalized by the cells and transported to the basolateral side of the monolayers. The PVs did not disrupt the epithelial barrier integrity nor did they modify the release of proinflammatory cytokines. In contrast, LMC from both fish species modified the physical and immunological properties of the epithelial barrier and the responses differed between bony and cartilaginous fish. While the barrier integrity was lowered by cod LMC 24 h after cell stimulation, it was increased by up to 2.3-fold by shark LMC. Furthermore, LMC from both fish species increased basolateral and apical release of IL-6 and IL-8, while CCL2 release was increased by cod but not by shark LMC. In summary, our study demonstrated the rapid transport of PVs across the epithelium which may result in their availability to antigen presenting cells required for allergic sensitization. Moreover, different cell responses to LMC derived from bony versus cartilaginous fish were observed, which may play a role in different allergenic potentials of these two fish classes.
鱼类加工工人的鱼类过敏患病率高于一般人群，这可能是由于通过吸入和更高的暴露而致敏。然而，支气管上皮细胞对鱼类过敏原的反应从未被探索过。来自硬骨鱼的副肌球蛋白（PVs）是鱼类过敏的主要致敏原，而软骨鱼类及其 PVs 被认为致敏性较低。越来越多的证据表明，除了过敏原源中的蛋白质之外，过敏原源中的其他成分，如花粉中的小于 3 kDa（LMC）的低分子量成分，可能在过敏致敏过程中充当佐剂。我们研究了支气管上皮细胞对来自硬骨鱼大西洋鳕鱼和软骨鱼鲨鱼的 PVs 和 LMC 的反应。用鱼类 PVs 和/或相应的鱼类 LMC 刺激支气管上皮细胞系 16HBE14o-的极化单层细胞的顶端。监测屏障完整性、PVs 穿过单层细胞的转运和介质的释放。来自硬骨鱼和软骨鱼的完整 PVs 被细胞迅速内化并转运到单层细胞的基底外侧。PVs 没有破坏上皮屏障的完整性，也没有改变促炎细胞因子的释放。相比之下，来自两种鱼类的 LMC 改变了上皮屏障的物理和免疫学特性，并且硬骨鱼和软骨鱼之间的反应不同。虽然鳕鱼 LMC 在细胞刺激后 24 小时降低了屏障完整性，但鲨鱼 LMC 可将其增加多达 2.3 倍。此外，来自两种鱼类的 LMC 均增加了 IL-6 和 IL-8 的基底外侧和顶端释放，而 CCL2 的释放则被鳕鱼 LMC 增加，而不是鲨鱼 LMC。总之，我们的研究表明，PVs 迅速穿过上皮细胞转运，这可能导致它们可用于过敏致敏所需的抗原呈递细胞。此外，还观察到源自硬骨鱼和软骨鱼的 LMC 对细胞的不同反应，这可能在这两种鱼类类别的不同致敏潜能中起作用。
