title: Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome.
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.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Scaccabarozzi
authors.affiliation: Rega Institute for Medical Research, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Deroost
authors.affiliation: Rega Institute for Medical Research, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Natacha
authors.initials: N
authors.lastname: Lays
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Omodeo Salè
authors.affiliation: Rega Institute for Medical Research, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Van den Steen
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008288:Malaria / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010962:Plasmodium berghei / Q000502:physiology; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology*
chemical_list: D008055:Lipids; D011663:Pulmonary Surfactants