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Vitronectin is produced in the lung upon infection by respiratory pathogens, and is utilized to evade the innate immunity

Paulsson, Magnus LU orcid ; Che, Karlhans Fru ; Ahl, Jonas LU ; Smith, Margaretha E. ; Qvarfordt, Ingemar ; Su, Yu-Ching LU ; Linden, Anders and Riesbeck, Kristian LU orcid (2017) 16th International Conference on Pseudomonas p.132-132
Abstract
Bacterial extracellular vesicles (EVs) are shed during growth by the respiratory pathogens Pseudomonas aeruginosa and Haemophilus influenzae. Vesicles trigger release of antimicrobial compounds and proteins of the complement, which are partly regulated by vitronectin. We hypothesized that vitronectin is elevated in the lungs during pneumonia, that respiratory epithelial cells produce vitronectin upon bacterial stimulation and that vitronectin is utilized by bacteria for increased virulence.
Vitronectin-concentrations were measured by ELISA in bronchoalveolar lavage fluid (BALF) from patients with pneumonia (n=8) and from healthy volunteers (n=13) with or without pulmonary endotoxin instillation. Elevated vitronectin concentrations were... (More)
Bacterial extracellular vesicles (EVs) are shed during growth by the respiratory pathogens Pseudomonas aeruginosa and Haemophilus influenzae. Vesicles trigger release of antimicrobial compounds and proteins of the complement, which are partly regulated by vitronectin. We hypothesized that vitronectin is elevated in the lungs during pneumonia, that respiratory epithelial cells produce vitronectin upon bacterial stimulation and that vitronectin is utilized by bacteria for increased virulence.
Vitronectin-concentrations were measured by ELISA in bronchoalveolar lavage fluid (BALF) from patients with pneumonia (n=8) and from healthy volunteers (n=13) with or without pulmonary endotoxin instillation. Elevated vitronectin concentrations were found in BALF collected during pneumonia compared to healthy individuals (p=0.0063) and in endotoxin-challenged pulmonary segments compared to control segments (after 12h: p=0.031; 48h: p=0.016). Flow cytometry revealed that bacteria captured vitronectin from BALF onto their surface and subsequently became less sensitive to killing by serum compared to controls (P. aeruginosa p=0.016, H. influenzae p=0.011). Increased levels of VTN mRNA after one hour (p=0.022) and increased surface bound vitronectin after 24h (p<0.001) were observed with type II bronchial alveolar epithelial cells (A549) after stimulation with EVs.
In conclusion, elevated vitronectin concentrations were found in BALF from patients with pneumonia and in healthy volunteers after pulmonary endotoxin instillation. Cellular experiments confirmed vitronectin production upon EV stimulation in vitro. Bacteria captured vitronectin from BALF on their surface to evade lysis by complement in serum. Hence, vitronectin is produced by epithelial cells upon bacterial infection and utilized by respiratory pathogens to persist in the respiratory tract. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to conference
publication status
published
subject
pages
132 - 132
conference name
16th International Conference on Pseudomonas
conference location
Liverpool, United Kingdom
conference dates
2017-09-05 - 2017-09-09
project
The Extracellular Matrix in Patients with CF or COPD as a Basis for Novel Therapeutical Opportunities
language
English
LU publication?
yes
id
0f5b3a4a-b5b7-4cd0-a5fa-bf2766fc87c4
alternative location
https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2017-16th-international-conference-on-pseudomonas.html#tab-2
date added to LUP
2019-06-20 09:31:25
date last changed
2020-01-28 14:04:09
@misc{0f5b3a4a-b5b7-4cd0-a5fa-bf2766fc87c4,
  abstract     = {{Bacterial extracellular vesicles (EVs) are shed during growth by the respiratory pathogens Pseudomonas aeruginosa and Haemophilus influenzae. Vesicles trigger release of antimicrobial compounds and proteins of the complement, which are partly regulated by vitronectin. We hypothesized that vitronectin is elevated in the lungs during pneumonia, that respiratory epithelial cells produce vitronectin upon bacterial stimulation and that vitronectin is utilized by bacteria for increased virulence.<br>
Vitronectin-concentrations were measured by ELISA in bronchoalveolar lavage fluid (BALF) from patients with pneumonia (n=8) and from healthy volunteers (n=13) with or without pulmonary endotoxin instillation. Elevated vitronectin concentrations were found in BALF collected during pneumonia compared to healthy individuals (p=0.0063) and in endotoxin-challenged pulmonary segments compared to control segments (after 12h: p=0.031; 48h: p=0.016). Flow cytometry revealed that bacteria captured vitronectin from BALF onto their surface and subsequently became less sensitive to killing by serum compared to controls (P. aeruginosa p=0.016, H. influenzae p=0.011). Increased levels of VTN mRNA after one hour (p=0.022) and increased surface bound vitronectin after 24h (p&lt;0.001) were observed with type II bronchial alveolar epithelial cells (A549) after stimulation with EVs.<br>
In conclusion, elevated vitronectin concentrations were found in BALF from patients with pneumonia and in healthy volunteers after pulmonary endotoxin instillation. Cellular experiments confirmed vitronectin production upon EV stimulation in vitro. Bacteria captured vitronectin from BALF on their surface to evade lysis by complement in serum. Hence, vitronectin is produced by epithelial cells upon bacterial infection and utilized by respiratory pathogens to persist in the respiratory tract.}},
  author       = {{Paulsson, Magnus and Che, Karlhans Fru and Ahl, Jonas and Smith, Margaretha E. and Qvarfordt, Ingemar and Su, Yu-Ching and Linden, Anders and Riesbeck, Kristian}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{132--132}},
  title        = {{Vitronectin is produced in the lung upon infection by respiratory pathogens, and is utilized to evade the innate immunity}},
  url          = {{https://microbiologysociety.org/event/society-events-and-meetings/focused-meeting-2017-16th-international-conference-on-pseudomonas.html#tab-2}},
  year         = {{2017}},
}