The role of leptin in the development of pulmonary neutrophilia in infection and acute lung injury.

Détails

ID Serval
serval:BIB_5D4EB799D5EB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The role of leptin in the development of pulmonary neutrophilia in infection and acute lung injury.
Périodique
Critical care medicine
Auteur⸱e⸱s
Ubags N.D., Vernooy J.H., Burg E., Hayes C., Bement J., Dilli E., Zabeau L., Abraham E., Poch K.R., Nick J.A., Dienz O., Zuñiga J., Wargo M.J., Mizgerd J.P., Tavernier J., Rincón M., Poynter M.E., Wouters E.F., Suratt B.T.
ISSN
1530-0293 (Electronic)
ISSN-L
0090-3493
Statut éditorial
Publié
Date de publication
02/2014
Peer-reviewed
Oui
Volume
42
Numéro
2
Pages
e143-51
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Résumé
One of the hallmarks of severe pneumonia and associated acute lung injury is neutrophil recruitment to the lung. Leptin is thought to be up-regulated in the lung following injury and to exert diverse effects on leukocytes, influencing both chemotaxis and survival. We hypothesized that pulmonary leptin contributes directly to the development of pulmonary neutrophilia during pneumonia and acute lung injury.
Controlled human and murine in vivo and ex vivo experimental studies.
Research laboratory of a university hospital.
Healthy human volunteers and subjects hospitalized with bacterial and H1N1 pneumonia. C57Bl/6 and db/db mice were also used.
Lung samples from patients and mice with either bacterial or H1N1 pneumonia and associated acute lung injury were immunostained for leptin. Human bronchoalveolar lavage samples obtained after lipopolysaccharide-induced lung injury were assayed for leptin. C57Bl/6 mice were examined after oropharyngeal aspiration of recombinant leptin alone or in combination with Escherichia coli- or Klebsiella pneumoniae-induced pneumonia. Leptin-resistant (db/db) mice were also examined using the E. coli model. Bronchoalveolar lavage neutrophilia and cytokine levels were measured. Leptin-induced chemotaxis was examined in human blood- and murine marrow-derived neutrophils in vitro.
Injured human and murine lung tissue showed leptin induction compared to normal lung, as did human bronchoalveolar lavage following lipopolysaccharide instillation. Bronchoalveolar lavage neutrophilia in uninjured and infected mice was increased and lung bacterial load decreased by airway leptin administration, whereas bronchoalveolar lavage neutrophilia in infected leptin-resistant mice was decreased. In sterile lung injury by lipopolysaccharide, leptin also appeared to decrease airspace neutrophil apoptosis. Both human and murine neutrophils migrated toward leptin in vitro, and this required intact signaling through the Janus Kinase 2/phosphatidylinositol-4,5-bisphosphate 3-kinase pathway.
We demonstrate that pulmonary leptin is induced in injured human and murine lungs and that this cytokine is effective in driving alveolar airspace neutrophilia. This action appears to be caused by direct effects of leptin on neutrophils.
Mots-clé
Acute Lung Injury/etiology, Animals, Female, Humans, Leptin/physiology, Leukocyte Disorders/etiology, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Neutrophils, Pneumonia, Bacterial/etiology, Pneumonia, Viral/etiology
Pubmed
Web of science
Création de la notice
29/04/2022 20:15
Dernière modification de la notice
30/04/2022 5:37
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