Christine Schorn, Christina Janko, Veit Krenn, Yi Zhao, Luis E. Munoz, Georg Schett, Martin Herrmann
Abstract
In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect of MSU crystals on blood granulocytes and analyze their contribution to granuloma formation and neutrophil extracellular traps (NETs) formation (NETosis) in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS)-dependent manner. Indeed, blocking ROS (e.g., the oxidative burst) by various anti-oxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonization of NETs, as a prerequisite for their clearance. The established dead cells' opsonins C3b, galectin-9, and CRP decorated the residual dead cells' corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (i) MSU crystals are strong inducers of ROS-dependent NETosis and (ii) that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement, and galectin-mediated phagocytic clearance.
Pharmacology, Toxicology and Pharmaceutical Science
3
4%
Other
6
7%
Unknown
13
16%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 January 2013.
All research outputs
#17,031,938
of 25,806,080 outputs
Outputs from Frontiers in immunology
#18,734
of 32,415 outputs
Outputs of similar age
#170,977
of 252,076 outputs
Outputs of similar age from Frontiers in immunology
#111
of 274 outputs
Altmetric has tracked 25,806,080 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
So far Altmetric has tracked 32,415 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
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We're also able to compare this research output to 274 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
