von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome

Sirima Kraisin, Sebastien Verhenne, Thao-Thy Pham, Kimberly Martinod, Claudia Tersteeg, Nele Vandeputte, Hans Deckmyn, Karen Vanhoorelbeke, Philippe E Van den Steen, Simon F De Meyer

Research output: Contribution to journalA1: Web of Science-articlepeer-review

Abstract

Background: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a lethal complication of severe malaria, characterized by marked pulmonary inflammation. Patient studies have suggested a link between von Willebrand factor (VWF) and malaria severity.

Objectives: To investigate the role of VWF in the pathogenesis of experimental MA-ARDS.

Methods: Plasmodium berghei NK65-E (PbNK65) parasites were injected in Vwf+/+ and Vwf-/- mice. Pathological parameters were assessed following infection.

Results: In accordance with patients with severe malaria, plasma VWF levels were increased and ADAMTS13 activity levels were reduced in experimental MA-ARDS. ADAMTS13- and plasmin-independent reductions of high molecular weight VWF multimers were observed at the end stage of disease. Thrombocytopenia was VWF-independent because it was observed in both Vwf+/+ and Vwf-/- mice. Interestingly, Vwf-/- mice had a shorter survival time compared with Vwf+/+ controls following PbNK65 infection. Lung edema could not explain this shortened survival because alveolar protein levels in Vwf-/- mice were approximately two times lower than in Vwf+/+ controls. Parasite load, on the other hand, was significantly increased in Vwf-/- mice compared with Vwf+/+ mice in both peripheral blood and lung tissue. In addition, anemia was only observed in PbNK65-infected Vwf-/- mice. Of note, Vwf-/- mice presented with two times more reticulocytes, a preferential target of the parasites.

Conclusions: This study suggests that parasite load together with malarial anemia, rather than alveolar leakage, might contribute to shortened survival in PbNK65-infected Vwf-/- mice. VWF deficiency is associated with early reticulocytosis following PbNK65 infection, which potentially explains the increase in parasite load.

Original languageEnglish
JournalJournal of Thrombosis and Haemostasis
Volume17
Issue number8
Pages (from-to)1372-1383
Number of pages12
ISSN1538-7836
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • ADAMTS13 Protein/blood
  • Anemia/blood
  • Animals
  • Disease Models, Animal
  • Female
  • Malaria/blood
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parasite Load
  • Plasmodium berghei/pathogenicity
  • Respiratory Distress Syndrome/blood
  • Reticulocytes/metabolism
  • Reticulocytosis
  • Thrombocytopenia/blood
  • von Willebrand Diseases/blood
  • von Willebrand Factor/genetics

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