Complexes between C-Reactive Protein and Very Low Density Lipoprotein Delay Bacterial Clearance in Sepsis

Cheng, Zhenxing, Abrams, Simon T, Toh, Julien, Wang, Susan S, Downey, Colin, Ge, Xiaoling, Yu, Qian, Yu, Weiping, Wang, Guozheng ORCID: 0000-0001-5525-3548 and Toh, Cheng-Hock (2020) Complexes between C-Reactive Protein and Very Low Density Lipoprotein Delay Bacterial Clearance in Sepsis. Journal of Immunology, 204 (10). pp. 2712-2721.

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Official URL: http://dx.doi.org/10.4049/jimmunol.1900962

Abstract

C-reactive protein (CRP) can increase up to 1000-fold in blood and form complexes with very low density lipoproteins (VLDL). These complexes are associated with worse outcomes for septic patients, and this suggests a potential pathological role in sepsis. Complex formation is heightened when CRP is over 200 mg/l and levels are associated with the severity of sepsis and blood bacterial culture positivity. Using a mouse bacteremia model, blood bacterial clearance can be delayed by i.v. injection of CRP-VLDL complexes. Complexes are more efficiently taken up by activated U937 cells in vitro and Kupffer cells in vivo than VLDL alone. Both in vitro-generated and naturally occurring CRP-VLDL complexes reduce phagocytosis of bacteria by activated U937 cells. Fcγ and scavenger receptors are involved and a competitive mechanism for clearance of CRP-VLDL complexes and bacteria is demonstrated. Interaction of phosphocholine groups on VLDL with CRP is the major driver for complex formation and phosphocholine can disrupt the complexes to reverse their inhibitory effects on phagocytosis and bacterial clearance. Increased formation of CRP-VLDL complexes is therefore harmful and could be a novel target for therapy in sepsis.

Item Type:	Article
Uncontrolled Keywords:	U937 Cells, Kupffer Cells, Animals, Mice, Inbred C57BL, Humans, Mice, Bacteremia, Sepsis, Disease Models, Animal, Phosphorylcholine, Lipoproteins, VLDL, C-Reactive Protein, Receptors, IgG, Phagocytosis, Protein Binding, Mutation, Aged, Middle Aged, Female, Male
Depositing User:	Symplectic Admin
Date Deposited:	02 Sep 2020 10:15
Last Modified:	18 Jan 2023 23:53
DOI:	10.4049/jimmunol.1900962
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3084578