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Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals

Pieterse, Elmar; Jeremic, Ivica; Czegley, Christine; Weidner, Daniela; Biermann, Mona H C; Veissi, Susan; Maueröder, Christian; Schauer, Christine; Bilyy, Rostyslav and Dumych, Tetiana, et al. (2016) In Scientific Reports 6.
Abstract

Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host. Here, we report that complement proteins and fetuins facilitate the continuous clearance by blood-borne phagocytes and resident macrophages of small urate microaggregates (UMA; <1 μm in size) that... (More)

Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host. Here, we report that complement proteins and fetuins facilitate the continuous clearance by blood-borne phagocytes and resident macrophages of small urate microaggregates (UMA; <1 μm in size) that initially form in hyperuricemic blood. If this clearance fails, UMA exhibit bipolar growth to form typical full-sized nsMSU with a size up to 100 μm. In contrast to UMA, nsMSU stimulated neutrophils to release NETs. Under conditions of flow, nsMSU and NETs formed densely packed DNase I-resistant tophus-like structures with a high obstructive potential, highlighting the importance of an adequate and rapid removal of UMA from the circulation. Under pathological conditions, intravascularly formed nsMSU may hold the key to the incompletely understood association between NET-driven cardiovascular disease and hyperuricemia.

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published
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Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:85002737182
ISSN
2045-2322
DOI
10.1038/srep38229
language
English
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no
id
c1fbb35b-c7d9-46e3-9527-75ce80892ae7
date added to LUP
2016-12-28 09:03:37
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2017-08-27 06:32:34
@article{c1fbb35b-c7d9-46e3-9527-75ce80892ae7,
  abstract     = {<p>Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host. Here, we report that complement proteins and fetuins facilitate the continuous clearance by blood-borne phagocytes and resident macrophages of small urate microaggregates (UMA; &lt;1 μm in size) that initially form in hyperuricemic blood. If this clearance fails, UMA exhibit bipolar growth to form typical full-sized nsMSU with a size up to 100 μm. In contrast to UMA, nsMSU stimulated neutrophils to release NETs. Under conditions of flow, nsMSU and NETs formed densely packed DNase I-resistant tophus-like structures with a high obstructive potential, highlighting the importance of an adequate and rapid removal of UMA from the circulation. Under pathological conditions, intravascularly formed nsMSU may hold the key to the incompletely understood association between NET-driven cardiovascular disease and hyperuricemia.</p>},
  articleno    = {38229},
  author       = {Pieterse, Elmar and Jeremic, Ivica and Czegley, Christine and Weidner, Daniela and Biermann, Mona H C and Veissi, Susan and Maueröder, Christian and Schauer, Christine and Bilyy, Rostyslav and Dumych, Tetiana and Hoffmann, Markus and Munoz, Luis E. and Bengtsson, Anders A. and Schett, Georg and Van Der Vlag, Johan and Herrmann, Martin},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals},
  url          = {http://dx.doi.org/10.1038/srep38229},
  volume       = {6},
  year         = {2016},
}