Growth Arrest-Specific Gene 6 product modulates innate immunity in sepsis

Détails

ID Serval
serval:BIB_8AC3405959F3
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Growth Arrest-Specific Gene 6 product modulates innate immunity in sepsis
Titre de la conférence
42nd Annual Scientific Meeting of the European Society for Clinical Investigation
Auteur(s)
Burnier L., Sugamele R., Leroy D., Roger T., Fumeaux T., Clauser S., Chanson M., Rignault S., Carmeliet P., Pugin J., Lemke G., Matsushima G. K., Earp H. S., Feihl F., Borgel D., Liaudet L., Chiolero R., Schapira M., Calandra T., Angelillo-Scherrer A.
Adresse
Geneva, Switzerland, March 26-29, 2008
ISBN
0014-2972
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
38
Série
European Journal of Clinical Investigation
Pages
43
Langue
anglais
Résumé
Background: Growth Arrest-Specific Gene 6 product (Gas6) is, like anticoagulant protein C, a vitamin K-dependent protein. Our aim was to determine whether Gas6 plays a role in sepsis.
Materials and methods: We submitted mice lacking Gas6 (Gas6)/)) or one of its receptors (Axl)/), Tyro3)/) or Mertk)/)) to LPS-induced endotoxemia and peritonitis (cecal ligation and puncture (CLP) and inoculation of E. coli). In addition, we measured Gas6 or its soluble receptors in plasma of eight volunteers that received LPS, 13 healthy subjects, 28 patients with severe sepsis, and 18 patients with non-infectious inflammatory diseases.
Results: Gas6 and its soluble receptor sAxl raised in mice models and TNF-a was more elevated in Gas6)/) mice than in wild-type (WT). Protein array showed that before and after LPS injection, titers of 62 cytokines were more elevated in plasma of Gas6)/) than WT mice. Endotoxemia-induced mortality was higher in Gas6)/), Axl)/), Tyro3)/) and Mertk)/) compared to WT mice and mortality subsequent to CLP was amplified in Gas6)/) mice. LPS-stimulated Gas6)/) macrophages produced more cytokines than WT macrophages. This production was dampened by recombinant Gas6. Phosphorylation of Akt in Gas6)/) macrophages was reduced, but p38 phosphorylation and NF-jB translocation were increased. In human, Gas6 raised in plasma after LPS (2 ng/kg). Gas6 and sAxl were higher in patients with severe sepsis than in healthy subjects or control patients, and there was a non-significant trend for higher Gas6 in the survival group.
Conclusions: Our data point to Gas6 as a major modulator of innate immunity and provide thereby novel insights into the mechanism of sepsis. Thus Gas6 and its receptors might constitute potential therapeutic targets for the development of new immunomodulating drugs.
Web of science
Création de la notice
30/09/2009 15:19
Dernière modification de la notice
03/03/2018 19:10
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