Preferential production and secretion of the complement regulator factor H-like protein 1 (FHL-1) by human myeloid cells
Immunobiology, vol. 228, pp. 152364
Abstract
Factor H is a pivotal complement regulatory protein that is preferentially produced by the liver and circulates in high concentrations in serum. There has been an increasing interest in the extrahepatic production of complement factors, including by cells of the immune system, since this contributes to non-canonical functions of local complement activation and regulation. Here we investigated the production and regulation of factor H and its splice variant factor H-like protein 1 (FHL-1) by human myeloid cells. As validation, we confirmed the predominant presence of intact factor H in serum, despite a strong but comparable mRNA expression of CFH and FHL1 in liver. Comparable levels of CFH and FHL1 were also observed in renal tissue, although a dominant staining for FHL-1 was shown within the proximal tubules. Human in vitro generated pro- and anti-inflammatory macrophages both expressed and produced factor H/FHL-1, but this was strongest in pro-inflammatory macrophages. Production was not affected by LPS activation, but was increased upon stimulation with IFN-γ or CD40L. Importantly, in both macrophage subsets mRNA expression of FHL1 was significantly higher than CFH. Moreover, production of FHL-1 protein could be confirmed using precipitation and immunoblotting of culture supernatants. These data identify macrophages as producers of factor H and FHL-1, thereby potentially contributing to local complement regulation at sites of inflammation.
Authors 12
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Mieke F. van Essen Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: m.f.van_essen@lumc.nl
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Emma T. M. Peereboom Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Nicole Schlagwein Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Daniëlle J. van Gijlswijk‐Janssen Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Tessa Nelemans Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Jivan V. Joeloemsingh Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Cathelijne W. van den Berg Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Jurriën Prins Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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University of Manchester · University of Tübingen
Affiliation as printed
Institute for Ophthalmic Research, Eberhard Karls University of Tübingen, Tübingen, Baden-Württemberg 72076, Germany; Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine & Health, University of Manchester, Manchester M13 9PL, United Kingdom
Institute for Ophthalmic Research, Eberhard Karls University of Tübingen, Tübingen, Baden-Württemberg 72076, Germany
Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine & Health, University of Manchester, Manchester M13 9PL, United Kingdom
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Affiliation as printed
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
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Cees van Kooten corresponding Aachen Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center Division of Nephrology and Transplant Medicine Department of Medicine, Leiden University Medical Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: c.van_kooten@lumc.nl
Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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