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

Pieterse E, Jeremic I, Czegley C, Weidner D, Biermann M, Veissi S, Maueröder C, Schauer C, Bilyy R, Dumych T, Hoffmann M, Munoz LE, Bengtsson AA, Schett G, Van Der Vlag J, Herrmann M, Munoz Becerra L (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 6

Pages Range: 38229

DOI: 10.1038/srep38229

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 ?m 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 ?m. 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.

Authors with CRIS profile

Mona Biermann Lehrstuhl für Biochemie und Molekulare Medizin Christian Maueröder Department of Medicine 3 – Rheumatology and Immunology Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Radboud University Nijmegen NL Netherlands (NL) Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького UA Ukraine (UA) Skåne University Hospital / Skånes universitetssjukhus SE Sweden (SE)

How to cite

APA:

Pieterse, E., Jeremic, I., Czegley, C., Weidner, D., Biermann, M., Veissi, S.,... Munoz Becerra, L. (2016). Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals. Scientific Reports, 6, 38229. https://doi.org/10.1038/srep38229

MLA:

Pieterse, Elmar, et al. "Blood-borne phagocytes internalize urate microaggregates and prevent intravascular NETosis by urate crystals." Scientific Reports 6 (2016): 38229.

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