Intravenous surfactant protein D inhibits lipopolysaccharide-induced systemic inflammation.
Collectin
Endotoxin shock
Inflammation
Lipopolysaccharide
Lung
Sepsis
Journal
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft
ISSN: 1618-0402
Titre abrégé: Ann Anat
Pays: Germany
ID NLM: 100963897
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
30
09
2022
revised:
27
12
2022
accepted:
03
01
2023
pmc-release:
01
04
2024
pubmed:
24
1
2023
medline:
8
3
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
Surfactant protein D (SP-D) is an innate host defense protein that clears infectious pathogens from the lung and regulates pulmonary host defense cells. SP-D is also detected in lower concentrations in plasma and many other non-pulmonary tissues. Plasma levels of SP-D increase during infection and other proinflammatory states; however, the source and functions of SP-D in the systemic circulation are largely unknown. We hypothesized that systemic SP-D may clear infectious pathogens and regulate host defense cells in extrapulmonary systems. To determine if SP-D inhibited inflammation induced by systemic lipopolysaccharide (LPS), E.coli LPS was administered to mice via tail vein injection with and without SP-D and the inflammatory response was measured. Systemic SP-D has a circulating half-life of 6 h. Systemic IL-6 levels in mice lacking the SP-D gene were similar to wild type mice at baseline but were significantly higher than wild type mice following LPS treatment (38,000 vs 29,900 ng/ml for 20 mg/kg LPS and 100,700 vs 73,700 ng/ml for 40 mg/kg LPS). In addition, treating wild type mice with purified intravenous SP-D inhibited LPS induced secretion of IL-6 and TNFα in a concentration dependent manner. Inhibition of LPS induced inflammation by SP-D correlated with SP-D LPS binding suggesting SP-D mediated inhibition of systemic LPS requires direct SP-D LPS interactions. Taken together, the above results suggest that circulating SP-D decreases systemic inflammation and raise the possibility that a physiological purpose of increasing systemic SP-D levels during infection is to scavenge systemic infectious pathogens and limit inflammation-induced tissue injury.
Sections du résumé
BACKGROUND
BACKGROUND
Surfactant protein D (SP-D) is an innate host defense protein that clears infectious pathogens from the lung and regulates pulmonary host defense cells. SP-D is also detected in lower concentrations in plasma and many other non-pulmonary tissues. Plasma levels of SP-D increase during infection and other proinflammatory states; however, the source and functions of SP-D in the systemic circulation are largely unknown. We hypothesized that systemic SP-D may clear infectious pathogens and regulate host defense cells in extrapulmonary systems.
METHODS
METHODS
To determine if SP-D inhibited inflammation induced by systemic lipopolysaccharide (LPS), E.coli LPS was administered to mice via tail vein injection with and without SP-D and the inflammatory response was measured.
RESULTS
RESULTS
Systemic SP-D has a circulating half-life of 6 h. Systemic IL-6 levels in mice lacking the SP-D gene were similar to wild type mice at baseline but were significantly higher than wild type mice following LPS treatment (38,000 vs 29,900 ng/ml for 20 mg/kg LPS and 100,700 vs 73,700 ng/ml for 40 mg/kg LPS). In addition, treating wild type mice with purified intravenous SP-D inhibited LPS induced secretion of IL-6 and TNFα in a concentration dependent manner. Inhibition of LPS induced inflammation by SP-D correlated with SP-D LPS binding suggesting SP-D mediated inhibition of systemic LPS requires direct SP-D LPS interactions.
CONCLUSIONS
CONCLUSIONS
Taken together, the above results suggest that circulating SP-D decreases systemic inflammation and raise the possibility that a physiological purpose of increasing systemic SP-D levels during infection is to scavenge systemic infectious pathogens and limit inflammation-induced tissue injury.
Identifiants
pubmed: 36690045
pii: S0940-9602(23)00003-1
doi: 10.1016/j.aanat.2023.152048
pmc: PMC9992088
mid: NIHMS1867208
pii:
doi:
Substances chimiques
Pulmonary Surfactant-Associated Protein D
0
Lipopolysaccharides
0
Interleukin-6
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152048Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL089505
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Kingma was previously a consultant and employee for Airway Therapeutics Inc which is currently developing surfactant protein D as a therapeutic agent. However, this relationship ended in 2021 and Dr. Kingma has no further financial or other interest in Airway Therapeutics Inc.
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