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Bacterial outer membrane vesicles induce vitronectin release into the bronchoalveolar space conferring protection from complement-mediated killing

Paulsson, Magnus LU orcid ; Che, Karlhans F. ; Ahl, Jonas LU ; Tham, Johan LU ; Sandblad, Linda ; Smith, Margaretha E. ; Qvarfordt, Ingemar ; Su, Yu Ching LU ; Lindén, Anders and Riesbeck, Kristian LU orcid (2018) In Frontiers in Microbiology 9(JUL).
Abstract

Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion. Vitronectin was analyzed in cell-free bronchoalveolar lavage fluid harvested from patients with pneumonia (n = 8) and from healthy volunteers after subsegmental endotoxin instillation (n = 13). Vitronectin... (More)

Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion. Vitronectin was analyzed in cell-free bronchoalveolar lavage fluid harvested from patients with pneumonia (n = 8) and from healthy volunteers after subsegmental endotoxin instillation (n = 13). Vitronectin binding by Pseudomonas aeruginosa and Haemophilus influenzae was analyzed, and subsequent complement evasion was assessed by serum challenge. The effects of outer membrane vesicles on vitronectin production in mouse lungs and human type II alveolar epithelial cells (A549) were determined. We detected increased vitronectin concentrations in lavage fluid during pneumonia (p = 0.0063) and after bronchial endotoxin challenge (p = 0.016). The capture of vitronectin by bacteria significantly reduced complement-mediated lysis. Following challenge with vesicles, vitronectin was detected in mouse bronchoalveolar space, and mouse alveolar epithelial cells in vivo as well as A549 cells in vitro contained increased levels of vitronectin. Taken together, outer membrane vesicles and endotoxin from Gram-negative bacteria induce vitronectin, which is released into the bronchoalveolar space, and used for evasion of complement-mediated clearance.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alveolar epithelial cells, Complement regulators, Endotoxin, Haemophilus influenzae, Immune evasion, Outer membrane vesicles, Pneumonia, Pseudomonas aeruginosa
in
Frontiers in Microbiology
volume
9
issue
JUL
article number
1559
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85049840858
ISSN
1664-302X
DOI
10.3389/fmicb.2018.01559
project
The Extracellular Matrix in Patients with CF or COPD as a Basis for Novel Therapeutical Opportunities
language
English
LU publication?
yes
id
eb2c281b-4541-4f1c-802a-cc4512fd6a3c
date added to LUP
2018-07-24 11:59:50
date last changed
2021-09-29 04:59:00
@article{eb2c281b-4541-4f1c-802a-cc4512fd6a3c,
  abstract     = {<p>Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion. Vitronectin was analyzed in cell-free bronchoalveolar lavage fluid harvested from patients with pneumonia (n = 8) and from healthy volunteers after subsegmental endotoxin instillation (n = 13). Vitronectin binding by Pseudomonas aeruginosa and Haemophilus influenzae was analyzed, and subsequent complement evasion was assessed by serum challenge. The effects of outer membrane vesicles on vitronectin production in mouse lungs and human type II alveolar epithelial cells (A549) were determined. We detected increased vitronectin concentrations in lavage fluid during pneumonia (p = 0.0063) and after bronchial endotoxin challenge (p = 0.016). The capture of vitronectin by bacteria significantly reduced complement-mediated lysis. Following challenge with vesicles, vitronectin was detected in mouse bronchoalveolar space, and mouse alveolar epithelial cells in vivo as well as A549 cells in vitro contained increased levels of vitronectin. Taken together, outer membrane vesicles and endotoxin from Gram-negative bacteria induce vitronectin, which is released into the bronchoalveolar space, and used for evasion of complement-mediated clearance.</p>},
  author       = {Paulsson, Magnus and Che, Karlhans F. and Ahl, Jonas and Tham, Johan and Sandblad, Linda and Smith, Margaretha E. and Qvarfordt, Ingemar and Su, Yu Ching and Lindén, Anders and Riesbeck, Kristian},
  issn         = {1664-302X},
  language     = {eng},
  month        = {07},
  number       = {JUL},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Microbiology},
  title        = {Bacterial outer membrane vesicles induce vitronectin release into the bronchoalveolar space conferring protection from complement-mediated killing},
  url          = {http://dx.doi.org/10.3389/fmicb.2018.01559},
  doi          = {10.3389/fmicb.2018.01559},
  volume       = {9},
  year         = {2018},
}