Expression of sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 in malaria-associated acute lung injury/acute respiratory distress syndrome in a mouse model.

Chuchard Punsawad,Parnpen Viriyavejakul,Olga A Sukocheva

doi:10.1371/journal.pone.0222098

Abstract

This study aimed to investigate the expression of sphingosine kinase 1 (SphK-1) and sphingosine 1-phosphate receptor 3 (S1PR-3) in a mouse model of malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS). DBA/2 mice were infected with Plasmodium berghei ANKA to generate an experimental model of malaria-associated ALI/ARDS. The infected mice were divided into 2 groups based on the histopathological study of lung tissues: those with and those without ALI/ARDS. The expression of the SphK-1 and S1PR-3 proteins in the lung tissues was investigated using immunohistochemical staining and Western blot analysis. In addition, the S1P level was quantified in plasma and lung tissues using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that the cellular expression of the SphK-1 and S1PR-3 proteins was significantly upregulated in endothelial cells, alveolar epithelial cells and alveolar macrophages in the lung tissues of malaria-infected mice with ALI/ARDS compared with those in the control groups. The increased expression of the SphK-1 and S1PR-3 proteins was confirmed using Western blot analysis. The concentration of S1P in plasma and lung tissues was significantly decreased in malaria-infected mice with ALI/ARDS compared with non-ALI/ARDS and control mice. Furthermore, increased expression of the SphK-1 and S1PR-3 proteins significantly correlated with lung injury scores and S1P concentrations in malaria-infected mice with ALI/ARDS. These findings highlight increased expression of SphK-1 and S1PR-3 in the lung tissues of malaria-infected mice with ALI/ARDS.

Highlights

According to the World Health Organization malaria report, there were 216 million malaria cases worldwide in 2016, leading to approximately 445,000 deaths [1]
The measurement of sphingosine and ceramide levels should be determined in the lung tissue and plasma samples to explain the functional role of sphingosine kinase 1 (SphK-1)/Sphingosine 1-phosphate (S1P) /sphingosine 1-phosphate receptor 3 (S1PR-3) pathway involved in the pathogenesis of malaria
This study provides new insights into the expression of sphingosine kinases (SphKs)-1 and S1PR-3 in P. berghei ANKA-infected DBA/2 mice with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)

Summary

Introduction

According to the World Health Organization malaria report, there were 216 million malaria cases worldwide in 2016, leading to approximately 445,000 deaths [1]. Several previous studies have reported that DBA/2 mice infected with Plasmodium berghei ANKA can develop ALI/ARDS, characterized by increased vascular endothelial growth factor (VEGF) and lung permeability, resulting in the development of pulmonary oedema and alveolar haemorrhage [3, 4]. Further study regarding the pathogenesis of malaria-associated ALI/ARDS demonstrated that haemozoin, the waste product of the Plasmodium protozoan, was associated with pulmonary complications, as evidenced by the increased levels of VEGF, proinflammatory chemokines, cytokines, and other inflammatory mediators in Plasmodium falciparum-derived haemozoin-injected mice [2, 3, 5, 6, 8]. Further studies are needed to provide important insights into the mechanisms involved in the pathogenesis of ALI/ARDS during malaria infection

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