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Peptide inhibition of acute lung injury in a novel two-hit rat model

Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secon...

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Autores principales: Sampson, Alana C., Lassiter, Brittany P., Gregory Rivera, Magdielis, Hair, Pamela S., Jackson, Kaitlyn G., Enos, Adrianne I., Vazifedan, Turaj, Werner, Alice L., Glesby, Marshall J., Lattanzio, Frank A., Cunnion, Kenji M., Krishna, Neel K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553074/
https://www.ncbi.nlm.nih.gov/pubmed/34710157
http://dx.doi.org/10.1371/journal.pone.0259133
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author Sampson, Alana C.
Lassiter, Brittany P.
Gregory Rivera, Magdielis
Hair, Pamela S.
Jackson, Kaitlyn G.
Enos, Adrianne I.
Vazifedan, Turaj
Werner, Alice L.
Glesby, Marshall J.
Lattanzio, Frank A.
Cunnion, Kenji M.
Krishna, Neel K.
author_facet Sampson, Alana C.
Lassiter, Brittany P.
Gregory Rivera, Magdielis
Hair, Pamela S.
Jackson, Kaitlyn G.
Enos, Adrianne I.
Vazifedan, Turaj
Werner, Alice L.
Glesby, Marshall J.
Lattanzio, Frank A.
Cunnion, Kenji M.
Krishna, Neel K.
author_sort Sampson, Alana C.
collection PubMed
description Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a ‘two-hit’ ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model.
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spelling pubmed-85530742021-10-29 Peptide inhibition of acute lung injury in a novel two-hit rat model Sampson, Alana C. Lassiter, Brittany P. Gregory Rivera, Magdielis Hair, Pamela S. Jackson, Kaitlyn G. Enos, Adrianne I. Vazifedan, Turaj Werner, Alice L. Glesby, Marshall J. Lattanzio, Frank A. Cunnion, Kenji M. Krishna, Neel K. PLoS One Research Article Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a ‘two-hit’ ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model. Public Library of Science 2021-10-28 /pmc/articles/PMC8553074/ /pubmed/34710157 http://dx.doi.org/10.1371/journal.pone.0259133 Text en © 2021 Sampson et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sampson, Alana C.
Lassiter, Brittany P.
Gregory Rivera, Magdielis
Hair, Pamela S.
Jackson, Kaitlyn G.
Enos, Adrianne I.
Vazifedan, Turaj
Werner, Alice L.
Glesby, Marshall J.
Lattanzio, Frank A.
Cunnion, Kenji M.
Krishna, Neel K.
Peptide inhibition of acute lung injury in a novel two-hit rat model
title Peptide inhibition of acute lung injury in a novel two-hit rat model
title_full Peptide inhibition of acute lung injury in a novel two-hit rat model
title_fullStr Peptide inhibition of acute lung injury in a novel two-hit rat model
title_full_unstemmed Peptide inhibition of acute lung injury in a novel two-hit rat model
title_short Peptide inhibition of acute lung injury in a novel two-hit rat model
title_sort peptide inhibition of acute lung injury in a novel two-hit rat model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553074/
https://www.ncbi.nlm.nih.gov/pubmed/34710157
http://dx.doi.org/10.1371/journal.pone.0259133
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