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Osteopontin protects against lung injury caused by extracellular histones

Kasetty, Gopinath LU ; Papareddy, Praveen LU ; Bhongir, Ravi K.V. LU ; Ali, Mohamad N. LU ; Mori, Michiko LU ; Wygrecka, Malgorzata; Erjefält, Jonas S. LU ; Hultgårdh-Nilsson, Anna; Palmberg, Lena and Herwald, Heiko LU , et al. (2019) In Mucosal Immunology 12(1). p.39-50
Abstract

Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and has been ascribed both pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may neutralize the harmful activities of extracellular histones at the airway mucosal surface. In a model of histone-induced acute lung injury, OPN−/− mice showed increased inflammation and tissue injury, and succumbed within 24 h, whereas wild-type mice showed lower degrees of inflammation and no mortality. In lipopolysaccharide-induced... (More)

Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and has been ascribed both pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may neutralize the harmful activities of extracellular histones at the airway mucosal surface. In a model of histone-induced acute lung injury, OPN−/− mice showed increased inflammation and tissue injury, and succumbed within 24 h, whereas wild-type mice showed lower degrees of inflammation and no mortality. In lipopolysaccharide-induced acute lung injury, wild-type mice showed less inflammation and tissue injury than OPN−/− mice. In bronchoalveolar lavage fluid from ARDS patients, high levels of OPN and also histone–OPN complexes were detected. In addition, OPN bound to histones with high affinity in vitro, resulting in less cytotoxicity and reduced formation of tissue-damaging neutrophil extracellular traps (NETs). The interaction between OPN and histones was dependent on posttranslational modification of OPN, i.e., phosphorylation. The findings demonstrate a novel role for OPN, modulating the pro-inflammatory and cytotoxic properties of free histones.

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Mucosal Immunology
volume
12
issue
1
pages
39 - 50
publisher
Nature Publishing Group
external identifiers
  • scopus:85052295647
ISSN
1933-0219
DOI
10.1038/s41385-018-0079-3
language
English
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yes
id
55c19171-17d5-43aa-a4a2-b2a97b389973
date added to LUP
2018-10-04 10:57:23
date last changed
2019-02-20 11:28:50
@article{55c19171-17d5-43aa-a4a2-b2a97b389973,
  abstract     = {<p>Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and has been ascribed both pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may neutralize the harmful activities of extracellular histones at the airway mucosal surface. In a model of histone-induced acute lung injury, OPN<sup>−/−</sup> mice showed increased inflammation and tissue injury, and succumbed within 24 h, whereas wild-type mice showed lower degrees of inflammation and no mortality. In lipopolysaccharide-induced acute lung injury, wild-type mice showed less inflammation and tissue injury than OPN<sup>−/−</sup> mice. In bronchoalveolar lavage fluid from ARDS patients, high levels of OPN and also histone–OPN complexes were detected. In addition, OPN bound to histones with high affinity in vitro, resulting in less cytotoxicity and reduced formation of tissue-damaging neutrophil extracellular traps (NETs). The interaction between OPN and histones was dependent on posttranslational modification of OPN, i.e., phosphorylation. The findings demonstrate a novel role for OPN, modulating the pro-inflammatory and cytotoxic properties of free histones.</p>},
  author       = {Kasetty, Gopinath and Papareddy, Praveen and Bhongir, Ravi K.V. and Ali, Mohamad N. and Mori, Michiko and Wygrecka, Malgorzata and Erjefält, Jonas S. and Hultgårdh-Nilsson, Anna and Palmberg, Lena and Herwald, Heiko and Egesten, Arne},
  issn         = {1933-0219},
  language     = {eng},
  number       = {1},
  pages        = {39--50},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {Osteopontin protects against lung injury caused by extracellular histones},
  url          = {http://dx.doi.org/10.1038/s41385-018-0079-3},
  volume       = {12},
  year         = {2019},
}