LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients
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 Japa...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520600359 |
| _version_ | 1818957090697248768 |
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| author | Auguste Dargent Jean-Paul Pais de Barros Samir Saheb Randa Bittar Wilfried Le Goff Alain Carrié Thomas Gautier Isabelle Fournel Anne Laure Rerole Hélène Choubley David Masson Laurent Lagrost Jean-Pierre Quenot |
| author_facet | Auguste Dargent Jean-Paul Pais de Barros Samir Saheb Randa Bittar Wilfried Le Goff Alain Carrié Thomas Gautier Isabelle Fournel Anne Laure Rerole Hélène Choubley David Masson Laurent Lagrost Jean-Pierre Quenot |
| author_sort | Auguste Dargent |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T11:04:20Z |
| format | Article |
| id | doaj.art-4750f967e5824c6684367f41a6b58339 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T11:04:20Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4750f967e5824c6684367f41a6b583392022-12-21T19:42:54ZengElsevierJournal of Lipid Research0022-22752020-12-01611217761783LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patientsAuguste Dargent0Jean-Paul Pais de Barros1Samir Saheb2Randa Bittar3Wilfried Le Goff4Alain Carrié5Thomas Gautier6Isabelle Fournel7Anne Laure Rerole8Hélène Choubley9David Masson10Laurent Lagrost11Jean-Pierre Quenot12Médecine Intensive Réanimation, Hôpital Edouard Herriot, Lyon, France; Université Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; For correspondence: Auguste DargentUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, FranceService d'endocrinologie et d'aphérèse, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, FranceService de Biochimie métabolique, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, FranceSorbonne University, INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Hôpital de la Pitié, Paris, FranceSorbonne University, INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Hôpital de la Pitié, Paris, France; Hôpitaux Universitaires Pitié-Salpêtrière/Charles-Foix, Department of Biochemistry for Endocrinology and Oncology, Obesity and Dyslipidemia Genetics Unit, Paris, FranceUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, FranceINSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, France; CHU Dijon-Bourgogne, Centre d'Investigation Clinique, Module Epidémiologie Clinique/Essais Cliniques, Dijon, FranceUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, FranceUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, FranceUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; Service de Biochimie médicale, CHU Dijon, Dijon, FranceUniversité Bourgogne Franche-Comté, LNC, Dijon, France; INSERM, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; Service de Biochimie médicale, CHU Dijon, Dijon, FranceFCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; INSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, France; CHU Dijon-Bourgogne, Centre d'Investigation Clinique, Module Epidémiologie Clinique/Essais Cliniques, Dijon, France; Médecine Intensive Réanimation, CHU Dijon, Dijon, FranceLipopolysaccharide (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.http://www.sciencedirect.com/science/article/pii/S0022227520600359lipoproteinslow density lipoproteintandem mass spectroscopyhuman and clinical researchinflammationsepsis |
| spellingShingle | Auguste Dargent Jean-Paul Pais de Barros Samir Saheb Randa Bittar Wilfried Le Goff Alain Carrié Thomas Gautier Isabelle Fournel Anne Laure Rerole Hélène Choubley David Masson Laurent Lagrost Jean-Pierre Quenot LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients Journal of Lipid Research lipoproteins low density lipoprotein tandem mass spectroscopy human and clinical research inflammation sepsis |
| title | LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients |
| title_full | LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients |
| title_fullStr | LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients |
| title_full_unstemmed | LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients |
| title_short | LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients |
| title_sort | ldl apheresis as an alternate method for plasma lps purification in healthy volunteers and dyslipidemic and septic patients |
| topic | lipoproteins low density lipoprotein tandem mass spectroscopy human and clinical research inflammation sepsis |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520600359 |
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