The uptake by blood-borne phagocytes of monosodium urate is dependent on heat-labile serum factor(s) and divalent cations

Abstract

Accumulation in tissues of post-apoptotic cells is a feature frequently observed in patients with systemic lupus erythematosus and in murine models of systemic autoimmune diseases. One of the endogenous danger molecules released by secondarily necrotic cells is monosodium urate (MSU), which is already established to be the causative agent of gout. Here, we show that MSU is taken up by eosinophils, neutrophils and monocytes in a process involving (a) heat-labile serum factor(s) and divalent cations. The uptake induces the release of the pro-inflammatory cytokines IL-1β/IL-18/TNFα and IL-6/IL-8 by monocytes and PMN, respectively.

Keywords::

• Inflammation
• SLE
• cytokines
• blood-borne phagocytes
• MSU

Declaration of interest: This work was supported by the intramural ELAN Fond 06.11.06.1 of the University Clinic of Erlangen and by the DFG (HE 4490/3–1). LM was supported by the SFB 643, and CS and CJ were supported by the training grant SFB GK643 and the K. und R. Wucherpfennigstiftung. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.