Abstract
Gout is caused by crystallization of uric acid in the form of monosodium urate (MSU) crystals, which induce a sterile inflammatory response that is hardly distinguishable from microbe-induced inflammatory responses. It is unclear, if MSU crystals (like microbes) are recognized by specific pattern recognition receptors. To identify possible soluble pattern recognition molecules for MSU crystals, we purified MSU-binding proteins from human body fluids. We identified C-reactive protein (CRP) as a major MSU-binding protein. Binding of CRP was strong enough to specifically deplete CRP from human serum. We found that CRP was required for fixation of complement components C1q, C1r, C1s and MASP1. Thus, we have identified a pattern recognition molecule for MSU crystals that links to the activation of complement. Notably, CRP does not show an even binding to the complete surface of the crystals. It rather binds to edges or distinct faces of the crystals.
Highlights
Gout is caused by crystallization of uric acid in the form of monosodium urate (MSU) crystals, which induce a sterile inflammatory response that is hardly distinguishable from microbe-induced inflammatory responses
The protein with the highest score in the band above 250 kDa was the known MSU crystal-binding protein apolipoprotein B, while in the 25 kDa band the protein with the highest score was C-reactive protein (CRP) (Fig. S1a)
In line with the results from the liquid chromatography-mass spectrometry (LC-MS) analysis the concentration of CRP in the body fluids was decreased after the incubation with MSU crystals, but not with zymosan (Fig. S1b), indicating CRP strongly binds to MSU crystals but not to zymosan
Summary
Gout is caused by crystallization of uric acid in the form of monosodium urate (MSU) crystals, which induce a sterile inflammatory response that is hardly distinguishable from microbe-induced inflammatory responses. It is unclear, if MSU crystals (like microbes) are recognized by specific pattern recognition receptors. To identify possible soluble pattern recognition molecules for MSU crystals, we purified MSU-binding proteins from human body fluids. Receptors CD16, CD11b and especially CD14 have been shown to be involved in MSU-induced inflammatory responses[11,12], while it is unclear if any of them recognize the crystals. In this study we purified MSU crystal binding proteins from human body fluids to identify potential soluble MSU recognition molecules
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