LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients.
Fiche publication
Date publication
décembre 2020
Journal
Journal of lipid research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FOURNEL Isabelle, Dr LAGROST Laurent, Dr PAIS DE BARROS Jean-Paul, Pr MASSON David
Tous les auteurs :
Dargent A, Pais de Barros JP, Saheb S, Bittar R, Le Goff W, Carrié A, Gautier T, Fournel I, Rerole AL, Choubley H, Masson D, Lagrost L, Quenot JP
Lien Pubmed
Résumé
Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.
Mots clés
human and clinical research, inflammation, lipopolysaccharide, lipoproteins, low density lipoprotein, low density lipoprotein apheresis, polymyxin hemoperfusion, sepsis, septic shock, tandem mass spectroscopy
Référence
J Lipid Res. 2020 Dec;61(12):1776-1783