Complement Factor H and Apolipoprotein E Participate in Regulation of Inflammation in THP-1 Macrophages

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Nissilä , E , Hakala , P , Leskinen , K , Roig , A , Syed , S , Van Kessel , K P M , Metso , J , De Haas , C J C , Saavalainen , P , Meri , S , Chroni , A , Van Strijp , J A G , Öörni , K , Jauhiainen , M , Jokiranta , T S & Haapasalo , K 2018 , ' Complement Factor H and Apolipoprotein E Participate in Regulation of Inflammation in THP-1 Macrophages ' , Frontiers in Immunology , vol. 9 , 2701 . https://doi.org/10.3389/fimmu.2018.02701

Title: Complement Factor H and Apolipoprotein E Participate in Regulation of Inflammation in THP-1 Macrophages
Author: Nissilä, Eija; Hakala, Pipsa; Leskinen, Katarzyna; Roig, Angela; Syed, Shahan; Van Kessel, Kok P. M.; Metso, Jari; De Haas, Carla J. C.; Saavalainen, Päivi; Meri, Seppo; Chroni, Angeliki; Van Strijp, Jos A. G.; Öörni, Katariina; Jauhiainen, Matti; Jokiranta, T. Sakari; Haapasalo, Karita
Contributor: University of Helsinki, Immunobiology Research Program
University of Helsinki, Immunobiology Research Program
University of Helsinki, Immunobiology Research Program
University of Helsinki, Immunomics
University of Helsinki, Immunobiology Research Program
University of Helsinki, Wihuri Research Institute
University of Helsinki, Medicum
University of Helsinki, Immunobiology Research Program
Date: 2018-11-21
Language: eng
Number of pages: 14
Belongs to series: Frontiers in Immunology
ISSN: 1664-3224
URI: http://hdl.handle.net/10138/268053
Abstract: The alternative pathway (AP) of complement is constantly active in plasma and can easily be activated on self surfaces and trigger local inflammation. Host cells are protected from AP attack by Factor H (FH), the main AP regulator in plasma. Although complement is known to play a role in atherosclerosis, the mechanisms of its contribution are not fully understood. Since FH via its domains 5-7 binds apoliporotein E (apoE) and macrophages produce apoE we examined how FH could be involved in the antiatherogenic effects of apoE. We used blood peripheral monocytes and THP-1 monocyte/macrophage cells which were also loaded with acetylated low-density lipoprotein (LDL) to form foam cells. Binding of FH and apoE on these cells was analyzed by flow cytometry. High-density lipoprotein (HDL)-mediated cholesterol efflux of activated THP-1 cells was measured and transcriptomes of THP-1 cells using mRNA sequencing were determined. We found that binding of FH to human blood monocytes and cholesterol-loaded THP-1 macrophages increased apoE binding to these cells. Preincubation of fluorescent cholesterol labeled THP-1 macrophages in the presence of FH increased cholesterol efflux and cholesterol-loaded macrophages displayed reduced transcription of proinflammatory/proatherogenic factors and increased transcription of anti-inflammatory/anti-atherogenic factors. Further incubation of THP-1 cells with serum reduced C3b/iC3b deposition. Overall, our data indicate that apoE and FH interact with monocytic cells in a concerted action and this interaction reduces complement activation and inflammation in the atherosclerotic lesions. By this way FH may participate in mediating the beneficial effects of apoE in suppressing atherosclerotic lesion progression.
Subject: complement
complement system
Factor H
apolipoprotein E
atherosclerosis
inflammation
HEMOLYTIC-UREMIC SYNDROME
DENSE DEPOSIT DISEASE
MACULAR DEGENERATION
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
PROTEIN BETA-1H
E SECRETION
HUMAN SERUM
A-I
ACTIVATION
CELLS
3111 Biomedicine
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