Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation
(2021) In Journal of Cystic Fibrosis 20(2). p.346-355- Abstract
BACKGROUND: Cystic fibrosis (CF), involves excessive airway accumulation of neutrophils, often in parallel with severe infection caused by Pseudomonas aeruginosa. Free histones are known to possess bactericidal properties, but the degree of antibacterial activity exerted on specific lung-based pathogens is largely unknown. Neutrophils have a high content of peptidyl deiminase 4 (PADI4), which citrullinate cationic peptidyl-arginines. In histone H3.1, several positions in the NH2-terminal tail are subject to citrullination.
METHODS: Full-length and segmented histone subunit H3.1 was investigated for bactericidal activity towards P. aeruginosa (strain PAO1). PADI4-induced citrullination of histone H3.1 was assessed for antibacterial... (More)
BACKGROUND: Cystic fibrosis (CF), involves excessive airway accumulation of neutrophils, often in parallel with severe infection caused by Pseudomonas aeruginosa. Free histones are known to possess bactericidal properties, but the degree of antibacterial activity exerted on specific lung-based pathogens is largely unknown. Neutrophils have a high content of peptidyl deiminase 4 (PADI4), which citrullinate cationic peptidyl-arginines. In histone H3.1, several positions in the NH2-terminal tail are subject to citrullination.
METHODS: Full-length and segmented histone subunit H3.1 was investigated for bactericidal activity towards P. aeruginosa (strain PAO1). PADI4-induced citrullination of histone H3.1 was assessed for antibacterial activity towards P. aeruginosa. Next, the effect of neutrophil elastase (NE)-mediated proteolysis of histone H3.1 was investigated. Finally, PADI4, H3.1, and citrullinated H3.1 were examined in healthy control and CF patient lung tissues.
RESULTS: Full-length histone H3.1 and sections of the histone H3.1 tail, displayed bactericidal activity towards P. aeruginosa. These antibacterial effects were reduced following citrullination by PADI4 or proteolysis by NE. Interestingly, citrullination of histone H3.1 exacerbated NE-mediated degradation. In CF lung tissue, citrullinated histone H3.1 and PADI4 immunoreactivity was abundant. Degraded histone H3.1 was detected in the sputum of CF patients but was absent in the sputum of healthy controls.
CONCLUSIONS: Citrullination impairs the antibacterial activity of histone H3.1 and exacerbates its proteolytic degradation by NE. Citrullination is likely to play an important role during resolution of acute inflammation. However, in chronic inflammation akin to CF, citrullination may dampen host defense and promote pathogen survival, as exemplified by P. aeruginosa.
(Less)
- author
- Tanner, Lloyd LU ; Bhongir, Ravi K V LU ; Karlsson, Christofer A Q LU ; Le, Sandy ; Ljungberg, Johanna K LU ; Andersson, Pia LU ; Andersson, Cecilia LU ; Malmström, Johan LU ; Egesten, Arne LU and Single, Andrew B LU
- organization
-
- Novel strategies targeting detrimental airway inflammation (research group)
- Respiratory Medicine, Allergology, and Palliative Medicine
- Respiratory Medicine and Allergology Research Group (research group)
- Infection Medicine Proteomics (research group)
- Infection Medicine (BMC)
- Airways, pathogens, innate immunity (research group)
- Respiratory Cell Biology (research group)
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Cystic Fibrosis
- volume
- 20
- issue
- 2
- pages
- 346 - 355
- publisher
- Elsevier
- external identifiers
-
- pmid:32727663
- scopus:85088793322
- ISSN
- 1873-5010
- DOI
- 10.1016/j.jcf.2020.07.010
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2020. Published by Elsevier B.V.
- id
- 3bb55e1f-e27c-4561-9750-b7259411990d
- date added to LUP
- 2020-07-31 19:47:12
- date last changed
- 2024-09-19 03:23:42
@article{3bb55e1f-e27c-4561-9750-b7259411990d, abstract = {{<p>BACKGROUND: Cystic fibrosis (CF), involves excessive airway accumulation of neutrophils, often in parallel with severe infection caused by Pseudomonas aeruginosa. Free histones are known to possess bactericidal properties, but the degree of antibacterial activity exerted on specific lung-based pathogens is largely unknown. Neutrophils have a high content of peptidyl deiminase 4 (PADI4), which citrullinate cationic peptidyl-arginines. In histone H3.1, several positions in the NH2-terminal tail are subject to citrullination.</p><p>METHODS: Full-length and segmented histone subunit H3.1 was investigated for bactericidal activity towards P. aeruginosa (strain PAO1). PADI4-induced citrullination of histone H3.1 was assessed for antibacterial activity towards P. aeruginosa. Next, the effect of neutrophil elastase (NE)-mediated proteolysis of histone H3.1 was investigated. Finally, PADI4, H3.1, and citrullinated H3.1 were examined in healthy control and CF patient lung tissues.</p><p>RESULTS: Full-length histone H3.1 and sections of the histone H3.1 tail, displayed bactericidal activity towards P. aeruginosa. These antibacterial effects were reduced following citrullination by PADI4 or proteolysis by NE. Interestingly, citrullination of histone H3.1 exacerbated NE-mediated degradation. In CF lung tissue, citrullinated histone H3.1 and PADI4 immunoreactivity was abundant. Degraded histone H3.1 was detected in the sputum of CF patients but was absent in the sputum of healthy controls.</p><p>CONCLUSIONS: Citrullination impairs the antibacterial activity of histone H3.1 and exacerbates its proteolytic degradation by NE. Citrullination is likely to play an important role during resolution of acute inflammation. However, in chronic inflammation akin to CF, citrullination may dampen host defense and promote pathogen survival, as exemplified by P. aeruginosa.</p>}}, author = {{Tanner, Lloyd and Bhongir, Ravi K V and Karlsson, Christofer A Q and Le, Sandy and Ljungberg, Johanna K and Andersson, Pia and Andersson, Cecilia and Malmström, Johan and Egesten, Arne and Single, Andrew B}}, issn = {{1873-5010}}, language = {{eng}}, number = {{2}}, pages = {{346--355}}, publisher = {{Elsevier}}, series = {{Journal of Cystic Fibrosis}}, title = {{Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation}}, url = {{http://dx.doi.org/10.1016/j.jcf.2020.07.010}}, doi = {{10.1016/j.jcf.2020.07.010}}, volume = {{20}}, year = {{2021}}, }