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Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice

Sercundes, Michelle K ; Ortolan, Luana S ; Debone, Daniela ; Soeiro-Pereira, Paulo V ; Gomes, Eliane ; Aitken, Elizabeth H ; Condino-Neto, Antonio ; Russo, Momtchilo ; D' Império Lima, Maria R ; Alvarez, José M ; Portugal, Silvia ; Marinho, Claudio R F ; Epiphanio, Sabrina Engwerda, Christian R.

PLoS pathogens, 2016-12, Vol.12 (12), p.e1006054 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice
Autor: Sercundes, Michelle K ; Ortolan, Luana S ; Debone, Daniela ; Soeiro-Pereira, Paulo V ; Gomes, Eliane ; Aitken, Elizabeth H ; Condino-Neto, Antonio ; Russo, Momtchilo ; D' Império Lima, Maria R ; Alvarez, José M ; Portugal, Silvia ; Marinho, Claudio R F ; Epiphanio, Sabrina
Engwerda, Christian R.
Assuntos: Acute Lung Injury - immunology ; Acute Lung Injury - microbiology ; Acute respiratory distress syndrome ; Adult respiratory distress syndrome ; Animals ; Biology and Life Sciences ; Care and treatment ; Complications and side effects ; Disease Models, Animal ; Extracellular Traps - immunology ; Fluorescent Antibody Technique ; Health aspects ; Malaria ; Malaria - complications ; Malaria - immunology ; Male ; Medicine and Health Sciences ; Mice ; Mice, Inbred DBA ; Neutrophils ; Neutrophils - immunology ; Polymerase Chain Reaction ; Prevention ; Research and Analysis Methods ; Respiratory Distress Syndrome, Adult - immunology ; Respiratory Distress Syndrome, Adult - microbiology ; Risk factors
É parte de: PLoS pathogens, 2016-12, Vol.12 (12), p.e1006054
Notas: The authors declare no commercial or other associations that might pose conflicts of interest.
Conceptualization: MKS SP CRFM SE. Formal analysis: MKS LSO DD PVSP. Funding acquisition: CRFM SE. Investigation: MKS LSO DD PVSP EG. Methodology: MKS LSO DD PVSP EG EHA. Project administration: CRFM SE. Resources: CRFM SE. Supervision: CRFM SE SP. Visualization: MKS SP CRFM SE. Writing – original draft: MKS SP CRFM SE. Writing – review & editing: JMA MRDL ACN MR SP.
Current address: Department of Medicine at Royal Melbourne Hospital, The University of Melbourne, Australia.
Descrição: Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS. Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications. In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species. We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury. The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival. This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria.
Editor: United States: Public Library of Science
Idioma: Inglês

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Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice

Sercundes, Michelle K ; Ortolan, Luana S ; Debone, Daniela ; Soeiro-Pereira, Paulo V ; Gomes, Eliane ; Aitken, Elizabeth H ; Condino-Neto, Antonio ; Russo, Momtchilo ; D' Império Lima, Maria R ; Alvarez, José M ; Portugal, Silvia ; Marinho, Claudio R F ; Epiphanio, Sabrina Engwerda, Christian R.

United States: Public Library of Science

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