Erickson N A, Gruber A D, Mundhenk L
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
J Comp Pathol. 2020 Jan;174:39-53. doi: 10.1016/j.jcpa.2019.10.193. Epub 2019 Nov 29.
Members of the chloride channel regulator, calcium-activated (CLCA) family are considered to be modifiers in inflammatory, mucus-based respiratory conditions such as asthma and cystic fibrosis. Previous work has shown substantial differences between human and murine CLCA orthologues that limit the value of mouse models. As an alternative, the cat is an unfamiliar but powerful model of human asthma. We therefore characterized the expression profiles of CLCA proteins in the feline respiratory tract. Identical to other species, the feline CLCA1 protein was immunohistochemically localized to virtually all goblet cells and found to be secreted into the mucus. However, it was not detected in submucosal glands where it is expressed in other species. In contrast to all other species studied to date, feline CLCA2 was not found in submucosal glands or any other airway cells. Similar to mice, but in contrast to man and pigs, the feline respiratory tract was devoid of CLCA4 expression. In the airways of asthmatic cats, CLCA1 was strongly overexpressed, similar to human patients. Therefore, despite some similarities in CLCA1 protein expression and secretion, substantial differences were identified between several feline CLCA family members and their respective orthologues in man, mice and pigs, which must be considered in comparative medicine.
氯离子通道调节剂家族成员、钙激活（CLCA）家族被认为是炎症性、基于黏液的呼吸道疾病（如哮喘和囊性纤维化）的调节因子。先前的研究表明，人类和小鼠的CLCA直系同源物之间存在显著差异，这限制了小鼠模型的价值。作为替代方案，猫是一种鲜为人知但强大的人类哮喘模型。因此，我们对猫呼吸道中CLCA蛋白的表达谱进行了表征。与其他物种相同，猫的CLCA1蛋白通过免疫组织化学定位到几乎所有杯状细胞，并发现其分泌到黏液中。然而，在其他物种中表达CLCA1蛋白的黏膜下腺中未检测到该蛋白。与迄今为止研究的所有其他物种不同，猫的CLCA2蛋白在黏膜下腺或任何其他气道细胞中均未发现。与小鼠相似，但与人类和猪不同，猫的呼吸道中没有CLCA4表达。在哮喘猫的气道中，CLCA1蛋白强烈过表达，与人类患者相似。因此，尽管CLCA1蛋白在表达和分泌方面存在一些相似之处，但在猫的几个CLCA家族成员与其在人类、小鼠和猪中的各自直系同源物之间发现了显著差异，在比较医学中必须考虑这些差异。
