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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-04-01
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| Series: | European Journal of Cell Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933522000176 |
| _version_ | 1818572127249367040 |
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| author | Idaira M. Guerrero-Fonseca Alexander García-Ponce Eduardo Vadillo Nathaniel L. Lartey Hilda Vargas-Robles Sandra Chánez-Paredes Ramón Castellanos-Martínez Porfirio Nava Abigail Betanzos Brittany M. Neumann Kinga Penkala-Auguste Craig T. Lefort Michael Schnoor |
| author_facet | Idaira M. Guerrero-Fonseca Alexander García-Ponce Eduardo Vadillo Nathaniel L. Lartey Hilda Vargas-Robles Sandra Chánez-Paredes Ramón Castellanos-Martínez Porfirio Nava Abigail Betanzos Brittany M. Neumann Kinga Penkala-Auguste Craig T. Lefort Michael Schnoor |
| author_sort | Idaira M. Guerrero-Fonseca |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T18:53:10Z |
| format | Article |
| id | doaj.art-e66f7c4b1adb45a384ba441a8e5d31de |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2024-12-14T18:53:10Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-e66f7c4b1adb45a384ba441a8e5d31de2022-12-21T22:51:11ZengElsevierEuropean Journal of Cell Biology0171-93352022-04-011012151214HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damageIdaira M. Guerrero-Fonseca0Alexander García-Ponce1Eduardo Vadillo2Nathaniel L. Lartey3Hilda Vargas-Robles4Sandra Chánez-Paredes5Ramón Castellanos-Martínez6Porfirio Nava7Abigail Betanzos8Brittany M. Neumann9Kinga Penkala-Auguste10Craig T. Lefort11Michael Schnoor12Department of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, MexicoDepartment of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, Mexico; Conacyt, Mexico City, MexicoBrown University Warren Alpert Medical School, Division of Surgical Research, Rhode Island Hospital, Providence, RI, USABrown University Warren Alpert Medical School, Division of Surgical Research, Rhode Island Hospital, Providence, RI, USABrown University Warren Alpert Medical School, Division of Surgical Research, Rhode Island Hospital, Providence, RI, USADepartment of Molecular Biomedicine, CINVESTAV-IPN, Avenida IPN 2508, 07360 Mexico City, Mexico; Correspondence to: Department for Molecular Biomedicine, CINVESTAV, Avenida IPN 2508, San Pedro Zacatenco, 07360 Mexico, DF, Mexico.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.http://www.sciencedirect.com/science/article/pii/S0171933522000176InflammationHCLSCortactinDiapedesisNeutrophil extravasationActin dynamics |
| spellingShingle | Idaira M. Guerrero-Fonseca Alexander García-Ponce Eduardo Vadillo Nathaniel L. Lartey Hilda Vargas-Robles Sandra Chánez-Paredes Ramón Castellanos-Martínez Porfirio Nava Abigail Betanzos Brittany M. Neumann Kinga Penkala-Auguste Craig T. Lefort Michael Schnoor HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage European Journal of Cell Biology Inflammation HCLS Cortactin Diapedesis Neutrophil extravasation Actin dynamics |
| 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 | Inflammation HCLS Cortactin Diapedesis Neutrophil extravasation Actin dynamics |
| url | http://www.sciencedirect.com/science/article/pii/S0171933522000176 |
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