Overexpression of Sphingosine Kinase-1 and Sphingosine-1-Phosphate Receptor-3 in Severe Malaria with Pulmonary Edema.

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.