Publication: Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin
Issued Date
2017-07-01
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19326203
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2-s2.0-85025481199
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS ONE. Vol.12, No.7 (2017)
Suggested Citation
Sitang Maknitikul, Natthanej Luplertlop, Georges E.R. Grau, Sumate Ampawong Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin. PLoS ONE. Vol.12, No.7 (2017). doi:10.1371/journal.pone.0181674 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41494
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Title
Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin
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Abstract
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution. A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined. Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging. The loss of EPCR and TM was primarily identified in ARDS patients and was related to the level of hemozoin, parasitized red blood cell (PRBC) and white blood cell accumulation in the lung. Moreover, an in vitro analysis demonstrated that interleukin-13 and -31 and hemozoin induced pneumocytic cell injury and apoptosis, as assessed by EB/AO staining, electron microscopy and the up-regulation of CARD-9 mRNA (caspase recruitment domain-9 messenger-ribonucleic acid). The dysregulation of EPCR and TM in the lung, especially in those with increased levels of hemozoin, may play an important role in the pathogenesis of malaria-associated ARDS through an apoptotic pathway.