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Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies

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Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. / Irmscher, Sarah; Brix, Silke R; Zipfel, Svante L H; Halder, Luke D; Mutlutürk, Sibel; Wulf, Sonia; Girdauskas, Evaldas; Reichenspurner, Hermann; Stahl, Rolf A K; Jungnickel, Berit; Wiech, Thorsten; Zipfel, Peter F; Skerka, Christine.

in: NAT COMMUN, Jahrgang 10, Nr. 1, 04.07.2019, S. 2961.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Irmscher, S, Brix, SR, Zipfel, SLH, Halder, LD, Mutlutürk, S, Wulf, S, Girdauskas, E, Reichenspurner, H, Stahl, RAK, Jungnickel, B, Wiech, T, Zipfel, PF & Skerka, C 2019, 'Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies', NAT COMMUN, Jg. 10, Nr. 1, S. 2961. https://doi.org/10.1038/s41467-019-10766-0

APA

Irmscher, S., Brix, S. R., Zipfel, S. L. H., Halder, L. D., Mutlutürk, S., Wulf, S., Girdauskas, E., Reichenspurner, H., Stahl, R. A. K., Jungnickel, B., Wiech, T., Zipfel, P. F., & Skerka, C. (2019). Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. NAT COMMUN, 10(1), 2961. https://doi.org/10.1038/s41467-019-10766-0

Vancouver

Irmscher S, Brix SR, Zipfel SLH, Halder LD, Mutlutürk S, Wulf S et al. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. NAT COMMUN. 2019 Jul 4;10(1):2961. https://doi.org/10.1038/s41467-019-10766-0

Bibtex

@article{59a7ec886a55432aa5ca7b3b1a9ee159,
title = "Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies",
abstract = "Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1β, TNFα, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.",
keywords = "C-Reactive Protein/metabolism, Complement C3b Inactivator Proteins/metabolism, Complement System Proteins/metabolism, Human Umbilical Vein Endothelial Cells/metabolism, Humans, Immobilized Proteins/metabolism, Inflammasomes/metabolism, Inflammation/metabolism, Inflammation Mediators/metabolism, Interleukin-1beta/metabolism, Lipoproteins, LDL/metabolism, Malondialdehyde/metabolism, Models, Biological, Monocytes/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Necrosis, Protein Binding, Receptors, G-Protein-Coupled/metabolism, Serum/metabolism, Type C Phospholipases/metabolism, Vascular Diseases/metabolism",
author = "Sarah Irmscher and Brix, {Silke R} and Zipfel, {Svante L H} and Halder, {Luke D} and Sibel Mutlut{\"u}rk and Sonia Wulf and Evaldas Girdauskas and Hermann Reichenspurner and Stahl, {Rolf A K} and Berit Jungnickel and Thorsten Wiech and Zipfel, {Peter F} and Christine Skerka",
year = "2019",
month = jul,
day = "4",
doi = "10.1038/s41467-019-10766-0",
language = "English",
volume = "10",
pages = "2961",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies

AU - Irmscher, Sarah

AU - Brix, Silke R

AU - Zipfel, Svante L H

AU - Halder, Luke D

AU - Mutlutürk, Sibel

AU - Wulf, Sonia

AU - Girdauskas, Evaldas

AU - Reichenspurner, Hermann

AU - Stahl, Rolf A K

AU - Jungnickel, Berit

AU - Wiech, Thorsten

AU - Zipfel, Peter F

AU - Skerka, Christine

PY - 2019/7/4

Y1 - 2019/7/4

N2 - Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1β, TNFα, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.

AB - Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1β, TNFα, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.

KW - C-Reactive Protein/metabolism

KW - Complement C3b Inactivator Proteins/metabolism

KW - Complement System Proteins/metabolism

KW - Human Umbilical Vein Endothelial Cells/metabolism

KW - Humans

KW - Immobilized Proteins/metabolism

KW - Inflammasomes/metabolism

KW - Inflammation/metabolism

KW - Inflammation Mediators/metabolism

KW - Interleukin-1beta/metabolism

KW - Lipoproteins, LDL/metabolism

KW - Malondialdehyde/metabolism

KW - Models, Biological

KW - Monocytes/metabolism

KW - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism

KW - Necrosis

KW - Protein Binding

KW - Receptors, G-Protein-Coupled/metabolism

KW - Serum/metabolism

KW - Type C Phospholipases/metabolism

KW - Vascular Diseases/metabolism

U2 - 10.1038/s41467-019-10766-0

DO - 10.1038/s41467-019-10766-0

M3 - SCORING: Journal article

C2 - 31273197

VL - 10

SP - 2961

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -