Abstract
Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine MA-ALI/ARDS and possibly contribute to lung dysfunction.
Highlights
According to the WHO classification, deep breathing, respiratory distress and pulmonary oedema are among the clinical features occurring in severe malaria accompanied by lung complications [1,2,3]
To deepen our understanding on the complexity of the pathological changes occurring during Malaria-associated acute lung injury (MA-ALI)/ARDS, we explored the biochemical modifications and lipid alterations of lung tissue and the molecular organization and lipid composition of alveolar surfactant in C57BL/6J mice infected with Plasmodium berghei NK65 (PbNK65), a well-established murine model of malaria-associated acute respiratory distress syndrome (MA-ARDS)
C57BL/6J mice were infected intraperitoneally with 104 red blood cells (RBCs) from mice infected with PbNK65 or Plasmodium chabaudi AS (PcAS) and the development of parasitemia was monitored over time
Summary
According to the WHO classification, deep breathing, respiratory distress and pulmonary oedema are among the clinical features occurring in severe malaria accompanied by lung complications [1,2,3]. Pulmonary Hz levels are significantly correlated with inflammation, increased lung weight and alveolar oedema in mice [15], and increasing amounts of Hz are observed on lung autopsies from African children with increasing disease severity [13]. An altered lipid profile and increased levels of lipoperoxidation end products have been found in plasma from patients with ARDS of different aetiologies, no data are available on MA-ARDS [18, 19]
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