Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Biomed Res Int. 2020 Feb 26;2020:3932569. doi: 10.1155/2020/3932569. eCollection 2020.
Pulmonary edema (PE) is a major cause of pulmonary manifestations of severe malaria and is usually associated with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The sphingosine kinase-1 (SphK-1)/sphingosine-1-phosphate receptor-3 (S1PR-3) pathway has recently been reported to affect the pathogenesis of lung injury, but the expression of these proteins in the lungs of severe malaria patients has not been investigated. The cellular expression of SphK-1 and S1PR-3 in lung tissues from autopsied patients with malaria was investigated using immunohistochemistry (IHC). Lung tissues from patients who died of severe malaria were classified into two groups based on histopathological findings: those with PE (18 patients) and those without PE (non-PE, 19 patients). Ten samples of normal lung tissues were used as the control group. The protein expression levels of SphK-1 and S1PR-3 were significantly upregulated in endothelial cells (ECs), alveolar epithelial cells, and alveolar macrophages (AMs) in the lungs of severe malaria patients with PE compared to those in the non-PE and control groups (all < 0.001). In addition, the SphK-1 and S1PR-3 expression levels were significantly positively correlated in pulmonary ECs ( = 0.922, < 0.001), alveolar epithelial cells ( = 0.995, < 0.001), and AMs ( = 0.969, < 0.001). In conclusion, both the SphK-1 and S1PR-3 proteins were overexpressed in the lung tissues of severe malaria patients with PE, suggesting that SphK-1 and S1PR-3 mediate the pathogenesis of PE in severe malaria. Targeting the regulation of SphK-1 and/or S1PR-3 may be an approach to treat pulmonary complications in severe patients.
肺水肿（PE）是严重疟疾肺部表现的主要原因，通常与急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）相关。最近有报道称，鞘氨醇激酶-1（SphK-1）/鞘氨醇-1-磷酸受体-3（S1PR-3）通路影响肺损伤的发病机制，但严重疟疾患者肺部这些蛋白的表达尚未被研究过。本研究采用免疫组织化学（IHC）方法检测尸检疟疾患者肺组织中 SphK-1 和 S1PR-3 的细胞表达。根据组织病理学发现，将死于严重疟疾的患者肺组织分为两组：有肺水肿（PE）的患者（18 例）和无肺水肿（非-PE，19 例）的患者。将 10 例正常肺组织样本作为对照组。与非-PE 组和对照组相比，PE 组严重疟疾患者的肺内皮细胞（ECs）、肺泡上皮细胞和肺泡巨噬细胞（AMs）中 SphK-1 和 S1PR-3 的蛋白表达水平明显上调（均<0.001）。此外，肺 ECs（ = 0.922，<0.001）、肺泡上皮细胞（ = 0.995，<0.001）和 AMs（ = 0.969，<0.001）中 SphK-1 和 S1PR-3 的表达水平呈显著正相关。总之，在严重疟疾合并 PE 患者的肺组织中，SphK-1 和 S1PR-3 蛋白均过度表达，提示 SphK-1 和 S1PR-3 介导了严重疟疾合并 PE 的发病机制。针对 SphK-1 和/或 S1PR-3 的调控可能是治疗严重疟疾患者肺部并发症的一种方法。
