Alveolar epithelium, besides exerting a key role in gas exchange and surfactant production, plays important functions in host defense and inflammation. Pathological conditions associated to alveolar dysfunction include Acute Respiratory Distress Syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

The use of predictive in vitro models of human alveolar epithelium is nowadays required for the study of disease mechanisms, as well as of pharmacokinetic parameters of pulmonary drugs delivery. Here, we employed a novel 3D model of human alveoli, namely EpiAlveolar™, consisting of primary alveolar epithelial cells, pulmonary endothelial cells and fibroblasts, that reflects properly the in vivo-like conditions.

In EpiAlveolar™ we performed a characterization of Organic Cation Transporters (OCTs and OCTNs) expression and activity and we found that OCTN2, OCT1 and OCT3 are expressed on the basolateral membrane; instead, ATB^0,+ transporter for cationic and neutral amino acids, which shares with OCTN2 the affinity for carnitine as substrate, is readily detectable and functional at the apical side. We also show that these transporters differentially interact with anticholinergic drugs. Overall, our findings reveal close similarities of EpiAlveolar™ with the tracheal/bronchial epithelium (EpiAirway™ model) and entrust this alveolar tissue as a potential tool for the screening of biopharmaceuticals molecules.

肺泡上皮除了在气体交换和表面活性剂产生中发挥关键作用外，还在宿主防御和炎症中发挥重要作用。与肺泡功能障碍相关的病理状况包括急性呼吸窘迫综合征 (ARDS)、哮喘、慢性阻塞性肺病 (COPD) 和特发性肺纤维化 (IPF)。

现在需要使用人类肺泡上皮的预测性体外模型来研究疾病机制以及肺部药物递送的药代动力学参数。在这里，我们采用了一种新型的人类肺泡 3D 模型，即 EpiAlveolar™，由原代肺泡上皮细胞、肺内皮细胞和成纤维细胞组成，可正确反映体内条件。

在 EpiAlveolar™ 中，我们对有机阳离子转运蛋白（OCT 和 OCTN）的表达和活性进行了表征，我们发现 OCTN2、OCT1 和 OCT3 在基底外侧膜上表达；相反，阳离子和中性氨基酸的ATB ^0,+转运蛋白与 OCTN2 具有对作为底物的肉碱的亲和力，在顶端很容易检测和起作用。我们还表明这些转运蛋白与抗胆碱能药物的相互作用不同。总体而言，我们的研究结果揭示了 EpiAlveolar™ 与气管/支气管上皮（EpiAirway™ 模型）的密切相似性，并委托这种肺泡组织作为筛选生物药物分子的潜在工具。