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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
R
Q
Acceso en línea:https://doaj.org/article/8baa0af460fe4141a2f2b97f94acace5
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:8baa0af460fe4141a2f2b97f94acace5
record_format dspace
spelling oai:doaj.org-article:8baa0af460fe4141a2f2b97f94acace52021-12-02T20:16:27ZPeptide inhibition of acute lung injury in a novel two-hit rat model.1932-620310.1371/journal.pone.0259133https://doaj.org/article/8baa0af460fe4141a2f2b97f94acace52021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259133https://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, p e0259133 (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/8baa0af460fe4141a2f2b97f94acace5
work_keys_str_mv AT alanacsampson peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT brittanyplassiter peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT magdielisgregoryrivera peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT pamelashair peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT kaitlyngjackson peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT adrianneienos peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT turajvazifedan peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT alicelwerner peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT marshalljglesby peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT frankalattanzio peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT kenjimcunnion peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
AT neelkkrishna peptideinhibitionofacutelunginjuryinanoveltwohitratmodel
_version_ 1718374479764127744