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HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage

Sepsis remains an important health problem worldwide due to inefficient treatments often resulting in multi-organ failure. Neutrophil recruitment is critical during sepsis. While neutrophils are required to combat invading bacteria, excessive neutrophil recruitment contributes to tissue damage due t...

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Autores principales: Guerrero-Fonseca, Idaira M., García-Ponce, Alexander, Vadillo, Eduardo, Lartey, Nathaniel L., Vargas-Robles, Hilda, Chánez-Paredes, Sandra, Castellanos-Martínez, Ramón, Nava, Porfirio, Betanzos, Abigail, Neumann, Brittany M., Penkala-Auguste, Kinga, Lefort, Craig T., Schnoor, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170315/
https://www.ncbi.nlm.nih.gov/pubmed/35286924
http://dx.doi.org/10.1016/j.ejcb.2022.151214
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author Guerrero-Fonseca, Idaira M.
García-Ponce, Alexander
Vadillo, Eduardo
Lartey, Nathaniel L.
Vargas-Robles, Hilda
Chánez-Paredes, Sandra
Castellanos-Martínez, Ramón
Nava, Porfirio
Betanzos, Abigail
Neumann, Brittany M.
Penkala-Auguste, Kinga
Lefort, Craig T.
Schnoor, Michael
author_facet Guerrero-Fonseca, Idaira M.
García-Ponce, Alexander
Vadillo, Eduardo
Lartey, Nathaniel L.
Vargas-Robles, Hilda
Chánez-Paredes, Sandra
Castellanos-Martínez, Ramón
Nava, Porfirio
Betanzos, Abigail
Neumann, Brittany M.
Penkala-Auguste, Kinga
Lefort, Craig T.
Schnoor, Michael
author_sort Guerrero-Fonseca, Idaira M.
collection PubMed
description Sepsis remains an important health problem worldwide due to inefficient treatments often resulting in multi-organ failure. Neutrophil recruitment is critical during sepsis. While neutrophils are required to combat invading bacteria, excessive neutrophil recruitment contributes to tissue damage due to their arsenal of molecular weapons that do not distinguish between host and pathogen. Thus, neutrophil recruitment needs to be fine-tuned to ensure bacterial killing, while avoiding neutrophil-inflicted tissue damage. We recently showed that the actin-binding protein HS1 promotes neutrophil extravasation; and hypothesized that HS1 is also a critical regulator of sepsis progression. We evaluated the role of HS1 in a model of lethal sepsis induced by cecal-ligation and puncture. We found that septic HS1-deficient mice had a better survival rate compared to WT mice due to absence of lung damage. Lungs of septic HS1-deficient mice showed less inflammation, fibrosis, and vascular congestion. Importantly, systemic CLP-induced neutrophil recruitment was attenuated in the lungs, the peritoneum and the cremaster in the absence of HS1. Lungs of HS1-deficient mice produced significantly more interleukin-10. Compared to WT neutrophils, those HS1-deficient neutrophils that reached the lungs had increased surface levels of Gr-1, ICAM-1, and L-selectin. Interestingly, HS1-deficient neutrophils had similar F-actin content and phagocytic activity, but they failed to polymerize actin and deform in response to CXCL-1 likely explaining the reduced systemic neutrophil recruitment in HS1-deficient mice. Our data show that HS1 deficiency protects against sepsis by attenuating neutrophil recruitment to amounts sufficient to combat bacterial infection, but insufficient to induce tissue damage.
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spelling pubmed-101703152023-05-10 HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage Guerrero-Fonseca, Idaira M. García-Ponce, Alexander Vadillo, Eduardo Lartey, Nathaniel L. Vargas-Robles, Hilda Chánez-Paredes, Sandra Castellanos-Martínez, Ramón Nava, Porfirio Betanzos, Abigail Neumann, Brittany M. Penkala-Auguste, Kinga Lefort, Craig T. Schnoor, Michael Eur J Cell Biol Article Sepsis remains an important health problem worldwide due to inefficient treatments often resulting in multi-organ failure. Neutrophil recruitment is critical during sepsis. While neutrophils are required to combat invading bacteria, excessive neutrophil recruitment contributes to tissue damage due to their arsenal of molecular weapons that do not distinguish between host and pathogen. Thus, neutrophil recruitment needs to be fine-tuned to ensure bacterial killing, while avoiding neutrophil-inflicted tissue damage. We recently showed that the actin-binding protein HS1 promotes neutrophil extravasation; and hypothesized that HS1 is also a critical regulator of sepsis progression. We evaluated the role of HS1 in a model of lethal sepsis induced by cecal-ligation and puncture. We found that septic HS1-deficient mice had a better survival rate compared to WT mice due to absence of lung damage. Lungs of septic HS1-deficient mice showed less inflammation, fibrosis, and vascular congestion. Importantly, systemic CLP-induced neutrophil recruitment was attenuated in the lungs, the peritoneum and the cremaster in the absence of HS1. Lungs of HS1-deficient mice produced significantly more interleukin-10. Compared to WT neutrophils, those HS1-deficient neutrophils that reached the lungs had increased surface levels of Gr-1, ICAM-1, and L-selectin. Interestingly, HS1-deficient neutrophils had similar F-actin content and phagocytic activity, but they failed to polymerize actin and deform in response to CXCL-1 likely explaining the reduced systemic neutrophil recruitment in HS1-deficient mice. Our data show that HS1 deficiency protects against sepsis by attenuating neutrophil recruitment to amounts sufficient to combat bacterial infection, but insufficient to induce tissue damage. 2022-04 2022-03-09 /pmc/articles/PMC10170315/ /pubmed/35286924 http://dx.doi.org/10.1016/j.ejcb.2022.151214 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Guerrero-Fonseca, Idaira M.
García-Ponce, Alexander
Vadillo, Eduardo
Lartey, Nathaniel L.
Vargas-Robles, Hilda
Chánez-Paredes, Sandra
Castellanos-Martínez, Ramón
Nava, Porfirio
Betanzos, Abigail
Neumann, Brittany M.
Penkala-Auguste, Kinga
Lefort, Craig T.
Schnoor, Michael
HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title_full HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title_fullStr HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title_full_unstemmed HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title_short HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
title_sort hs1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170315/
https://www.ncbi.nlm.nih.gov/pubmed/35286924
http://dx.doi.org/10.1016/j.ejcb.2022.151214
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