Original Research ARTICLE
Complement factor H and apolipoprotein E participate in regulation of inflammation in THP-1 macrophages
- 1Department of Bacteriology and Immunology, Faculty of Medicine, University of Helsinki, Finland
- 2Department of Medical Microbiology, University Medical Center Utrecht, Netherlands
- 3Minerva Foundation Institute for Medical Research, Finland
- 4Institute of Biosciences and Applications, National Centre of Scientific Research Demokritos, Greece
- 5Wihuri Research Institute, Finland
- 6Department of Bacteriology and Immunology, and Research Programs Unit, University of Helsinki, Finland
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 analysed 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.
Keywords: Complement - immunological terms, complement system, factor H, Apolipoprotein E, atheroscelorsis, Inflammation
Received: 21 Aug 2018;
Accepted: 01 Nov 2018.
Edited by:Nicole Thielens, UMR5075 Institut de Biologie Structurale (IBS), France
Reviewed by:Lubka T. Roumenina, INSERM U1138 Centre de Recherche des Cordeliers, France
Harald F. Langer, University of Tubingen, Germany
Copyright: © 2018 Nissilä, Hakala, Leskinen, Roig, Syed, van Kessel, Metso, de Haas, Saavalainen, Meri, Chroni, Van Strijp, Öörni, Jauhiainen, Jokiranta and Haapasalo-Tuomainen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Karita Haapasalo-Tuomainen, University of Helsinki, Department of Bacteriology and Immunology, and Research Programs Unit, Helsinki, Finland, email@example.com