Recombinant human plasma phospholipid transfer protein (PLTP) to prevent bacterial growth and to treat sepsis.
Fiche publication
Date publication
juin 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAGROST Laurent, Pr MASSON David
Tous les auteurs :
Deckert V, Lemaire S, Ripoll PJ, de Barros JP, Labbé J, Borgne CC, Turquois V, Maquart G, Larose D, Desroche N, Ménétrier F, Le Guern N, Lebrun LJ, Desrumaux C, Gautier T, Grober J, Thomas C, Masson D, Houdebine LM, Lagrost L
Lien Pubmed
Résumé
Although plasma phospholipid transfer protein (PLTP) has been mainly studied in the context of atherosclerosis, it shares homology with proteins involved in innate immunity. Here, we produced active recombinant human PLTP (rhPLTP) in the milk of new lines of transgenic rabbits. We successfully used rhPLTP as an exogenous therapeutic protein to treat endotoxemia and sepsis. In mouse models with injections of purified lipopolysaccharides or with polymicrobial infection, we demonstrated that rhPLTP prevented bacterial growth and detoxified LPS. In further support of the antimicrobial effect of PLTP, PLTP-knocked out mice were found to be less able than wild-type mice to fight against sepsis. To our knowledge, the production of rhPLTP to counter infection and to reduce endotoxemia and its harmful consequences is reported here for the first time. This paves the way for a novel strategy to satisfy long-felt, but unmet needs to prevent and treat sepsis.
Mots clés
Animals, Anti-Infective Agents, pharmacology, Mice, Mice, Inbred C57BL, Phospholipid Transfer Proteins, pharmacology, Rabbits, Recombinant Proteins, pharmacology, Sepsis, drug therapy
Référence
Sci Rep. 2017 Jun;7(1):3053