BernheimV1, Hal, Corpus, bibRecord, 000110

Physico-chemistry of lipopolysaccharides and inflammatory response : role of lipoproteins

Identifieur interne : 000110 ( Hal/Corpus ); précédent : 000109; suivant : 000111

Physico-chemistry of lipopolysaccharides and inflammatory response : role of lipoproteins

Auteurs : Wahib Sali

Source :

RBID : Hal:tel-01134149

Descripteurs français

mix :
- Agrégation, Dosage LC-MS/MS, Immunité innée, Inflammation, Lipide A, Lipopolysaccharide (LPS), Lipoprotéine, Monocyte, Protéine de Transfert des Phospholipides (PLTP), TLR4 (Toll-Like Receptor 4).

English descriptors

mix :
- Aggregation, Innate immunity, LC-MS/MS assay, Lipoprotein, PhosphoLipid Transfer Protein (PLTP).

Abstract

LPS is a potent bacterial pro-inflammatory agent, consisting of hydrophilic, polysaccharide part and of a lipid A which is considered like active moiety. Nevertheless, the O chain of LPS influences their aggregation in aqueous media. Therefore, our goal has been to determine the role of O chain on the LPS biological and physiopathological effects. Our work was organized according to three main axes, and led to the following findings :- development of a new LPS assay by LC-MS/MS. The combination of this new technique with LAL test allowed us to calculate an inactivation ratio which reflects the ability of host organism to inactivate LPS, especially through their transfer to HDL by PLTP. The ratio could be useful in predicting outcome of high risk patients.- the length of O chain modulates LPS-induced inflammation. Above their critical aggregation concentration, LPS form aggregates with an architecture and physiochemical properties dependent on their O chain. Both parameters determine LPS biological activity and their metabolism.- development of an innovative dual labelling of LPS as a new tool to explore LPS elimination pathway : the reverse LPS transport. This work brings evidence that the physiopathological effects of LPS depend on two parameters : their biological activity and their metabolism. Any strategy of research or therapeutic targeting LPS should take into account their molecular structure, their aggregability and the relation between the both parameters, which are major determinants of their biological activity and their metabolism.

Url:

https://tel.archives-ouvertes.fr/tel-01134149

Links to Exploration step

Hal:tel-01134149

Le document en format XML

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<term>Lipopolysaccharide (LPS)</term>
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<front><div type="abstract" xml:lang="en">LPS is a potent bacterial pro-inflammatory agent, consisting of hydrophilic, polysaccharide part and of a lipid A which is considered like active moiety. Nevertheless, the O chain of LPS influences their aggregation in aqueous media. Therefore, our goal has been to determine the role of O chain on the LPS biological and physiopathological effects.  Our work was organized according to three main axes, and led to the following findings :- development of a new LPS assay by LC-MS/MS. The combination of this new technique with LAL test allowed us to calculate an inactivation ratio which reflects the ability of host organism to inactivate LPS, especially through their transfer to HDL by PLTP. The ratio could be useful in predicting outcome of high risk patients.- the length of O chain modulates LPS-induced inflammation. Above their critical aggregation concentration, LPS form aggregates with an architecture and physiochemical properties dependent on their O chain. Both parameters determine LPS biological activity and their metabolism.- development of an innovative dual labelling of LPS as a new tool to explore LPS elimination pathway : the reverse LPS transport.  This work brings evidence that the physiopathological effects of LPS depend on two parameters : their biological activity and their metabolism.  Any strategy of research or therapeutic targeting LPS should take into account their molecular structure, their aggregability and the relation between the both parameters, which are major determinants of their biological activity and their metabolism.</div>
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            <abstract xml:lang="en">LPS is a potent bacterial pro-inflammatory agent, consisting of hydrophilic, polysaccharide part and of a lipid A which is considered like active moiety. Nevertheless, the O chain of LPS influences their aggregation in aqueous media. Therefore, our goal has been to determine the role of O chain on the LPS biological and physiopathological effects.  Our work was organized according to three main axes, and led to the following findings :- development of a new LPS assay by LC-MS/MS. The combination of this new technique with LAL test allowed us to calculate an inactivation ratio which reflects the ability of host organism to inactivate LPS, especially through their transfer to HDL by PLTP. The ratio could be useful in predicting outcome of high risk patients.- the length of O chain modulates LPS-induced inflammation. Above their critical aggregation concentration, LPS form aggregates with an architecture and physiochemical properties dependent on their O chain. Both parameters determine LPS biological activity and their metabolism.- development of an innovative dual labelling of LPS as a new tool to explore LPS elimination pathway : the reverse LPS transport.  This work brings evidence that the physiopathological effects of LPS depend on two parameters : their biological activity and their metabolism.  Any strategy of research or therapeutic targeting LPS should take into account their molecular structure, their aggregability and the relation between the both parameters, which are major determinants of their biological activity and their metabolism.</abstract>
            <abstract xml:lang="fr">Le LPS est un puissant agent pro-inflammatoire bactérien, dont la partie lipide A est considérée comme le principe actif. Néanmoins, la chaîne O des LPS influence leur agrégation en solution aqueuse. Notre but a été de déterminer le rôle de la chaîne O sur les effets biologiques et physiopathologiques des LPS.Nos travaux, menés selon trois axes stratégiques complémentaires, ont donné lieu aux avancées suivantes :- développement d'un dosage innovant des LPS par LC-MS/MS et d'un ratio d'inactivation des LPS sur la base d'une utilisation combinée dudit dosage et du test LAL. Ce ratio traduit la capacité d'un organisme hôte à inactiver les LPS, notamment par leur transfert aux HDL par la PLTP. Ce ratio pourrait être utile dans l'évaluation des patients à haut risque.- la longueur de la chaîne O module l'inflammation induite par les LPS. Au-delà de leur concentration d'agrégation critique, les LPS forment des agrégats dotés d’une architecture et de propriétés physico-chimiques dépendant de leur chaîne O. Ces deux paramètres déterminent l'activité biologique des LPS et leur métabolisme ;- développement d'un double marquage innovant des LPS confirmant leur voie principale d'élimination : le transport inverse du LPS.  Ce travail définit donc les effets physiopathologiques induits par les LPS comme résultant de deux composantes : leur activité biologique et leur métabolisme.  Toute stratégie de recherche ou thérapeutique ciblant les LPS, devrait donc prendre en compte leur structure moléculaire, leur agrégabilité et la relation entre ces deux paramètres, déterminants majeurs de l'activité biologique des LPS et de leur métabolisme.</abstract>
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Physico-chemistry of lipopolysaccharides and inflammatory response : role of lipoproteins

Physico-chemistry of lipopolysaccharides and inflammatory response : role of lipoproteins

Source :

Descripteurs français

English descriptors

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri