Complement Factor H and Apolipoprotein E Participate in Regulation of Inflammation in THP-1 Macrophages
| Autor: | Karita Haapasalo, Shahan Syed, Seppo Meri, Katarzyna Leskinen, Pipsa Hakala, Angeliki Chroni, T. Sakari Jokiranta, Carla J. C. de Haas, Angela Roig, Matti Jauhiainen, Päivi Saavalainen, Jari Metso, Eija Nissilä, Katariina Öörni, Kok P. M. van Kessel, Jos A. G. van Strijp |
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| Přispěvatelé: | Immunobiology Research Program, Department of Bacteriology and Immunology, Medicum, Research Programs Unit, University of Helsinki, Immunomics, Seppo Meri / Principal Investigator |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Transcription Genetic THP-1 Cells Monocytes ACTIVATION 0302 clinical medicine Immunology and Allergy complement Original Research apolipoprotein E DENSE DEPOSIT DISEASE Chemistry Cell biology A-I medicine.anatomical_structure Complement Factor H 030220 oncology & carcinogenesis Factor H Complement C3b E SECRETION lipids (amino acids peptides and proteins) medicine.symptom Lipoproteins HDL HUMAN SERUM lcsh:Immunologic diseases. Allergy Immunology Inflammation Proinflammatory cytokine 03 medical and health sciences Apolipoproteins E medicine Humans complement system Monocyte MACULAR DEGENERATION Complement system 030104 developmental biology MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS inflammation CELLS Alternative complement pathway iC3b HEMOLYTIC-UREMIC SYNDROME 3111 Biomedicine atherosclerosis lcsh:RC581-607 Foam Cells PROTEIN BETA-1H |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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