Natural antibodies and CRP drive anaphylatoxin production by urate crystals.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 03 2022
16 03 2022
Historique:
received:
31
10
2021
accepted:
28
02
2022
entrez:
17
3
2022
pubmed:
18
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
In gout, crystallization of uric acid in the form of monosodium urate (MSU) leads to a painful inflammatory response. MSU crystals induce inflammation by activating the complement system and various immune cell types, and by inducing necrotic cell death. We previously found that the soluble pattern recognition molecule C-reactive protein (CRP) recognizes MSU crystals, while enhancing complement activation. In the absence of CRP, MSU crystals still induced complement activation, suggesting additional CRP-independent mechanisms of complement activation. In the present study, we searched for additional MSU crystal-binding complement activators. We found that all healthy individuals, even unborn children, have MSU crystal-specific immunoglobulin M (IgM) in their blood. This indicates that innate IgM, also known as natural IgM, recognizes these crystals. In serum lacking IgM and CRP, MSU crystals showed negligible complement activation as assessed by the production of the anaphylatoxins C4a, C3a, and C5a (listed in order of production via the classical complement pathway). We show that IgM and CRP both activate the classical complement pathway on MSU crystals. CRP was more efficient at fixating active C1 on the crystals and inducing release of the most inflammatory anaphylatoxin C5a, indicating non-redundant functions of CRP. Notably, while CRP recognizes MSU crystals but not the related calcium pyrophosphate dihydrate (CPPD) crystals, natural IgM bound to both, suggesting common and distinct mechanisms of recognition of individual crystal types by complement activators.
Identifiants
pubmed: 35296708
doi: 10.1038/s41598-022-08311-z
pii: 10.1038/s41598-022-08311-z
pmc: PMC8924570
doi:
Substances chimiques
Anaphylatoxins
0
CRP protein, human
0
Immunoglobulin M
0
Receptors, Immunologic
0
Uric Acid
268B43MJ25
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4483Informations de copyright
© 2022. The Author(s).
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