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:	Alana C. Sampson, Brittany P. Lassiter, Magdielis Gregory Rivera, Pamela S. Hair, Kaitlyn G. Jackson, Adrianne I. Enos, Turaj Vazifedan, Alice L. Werner, Marshall J. Glesby, Frank A. Lattanzio, Kenji M. Cunnion, Neel K. Krishna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b02463b137f43bab72a43df0d2d248d
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spelling	oai:doaj.org-article:4b02463b137f43bab72a43df0d2d248d2021-11-04T06:49:37ZPeptide inhibition of acute lung injury in a novel two-hit rat model1932-6203https://doaj.org/article/4b02463b137f43bab72a43df0d2d248d2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553074/?tool=EBIhttps://doaj.org/toc/1932-6203Acute 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.Alana C. SampsonBrittany P. LassiterMagdielis Gregory RiveraPamela S. HairKaitlyn G. JacksonAdrianne I. EnosTuraj VazifedanAlice L. WernerMarshall J. GlesbyFrank A. LattanzioKenji M. CunnionNeel K. KrishnaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alana C. Sampson Brittany P. Lassiter Magdielis Gregory Rivera Pamela S. Hair Kaitlyn G. Jackson Adrianne I. Enos Turaj Vazifedan Alice L. Werner Marshall J. Glesby Frank A. Lattanzio Kenji M. Cunnion Neel K. Krishna Peptide inhibition of acute lung injury in a novel two-hit rat model
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.
format	article
author	Alana C. Sampson Brittany P. Lassiter Magdielis Gregory Rivera Pamela S. Hair Kaitlyn G. Jackson Adrianne I. Enos Turaj Vazifedan Alice L. Werner Marshall J. Glesby Frank A. Lattanzio Kenji M. Cunnion Neel K. Krishna
author_facet	Alana C. Sampson Brittany P. Lassiter Magdielis Gregory Rivera Pamela S. Hair Kaitlyn G. Jackson Adrianne I. Enos Turaj Vazifedan Alice L. Werner Marshall J. Glesby Frank A. Lattanzio Kenji M. Cunnion Neel K. Krishna
author_sort	Alana C. Sampson
title	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_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_sort	peptide inhibition of acute lung injury in a novel two-hit rat model
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4b02463b137f43bab72a43df0d2d248d
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Peptide inhibition of acute lung injury in a novel two-hit rat model

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