Renal Mast Cell recruitment in MRL/lpr mice (173.28)

Abstract Mast cells (MC) are key effectors cells of the immune system. MC infiltration has been reported in a variety of renal diseases including lupus nephritis. Recently it has been argued that MCs are key contributors to a common pathway of progressive renal injury, however, the chemotaxic mechanism of renal MC recruitment are largely unknown. We observed a progressive age-depended MC infiltrate in kidneys of MRL/lpr mice. MRL/lpr bone marrow-derived MC (BMMC) had a high chemotatic capacity in response to MRL/lpr serum. In order to characterize the factors involved in MCs recruitment in MRL/lpr mice we performed expression array analysis in stimulated and un-stimulated MRL/lpr MCs. Serum stimulation increased BMMC expression of the integrin alpha E and chemokine receptors CCR5 and CXCR4. Kidney immunofluorescence staining confirmed these finding in situ. BMMC chemotaxis in vitro was enhanced in response to CCR5 ligands (MIP-1α and RANTES) and CXCR4 ligand (SDF-1) and was blocked by using a non-peptide chemokine receptor antagonist TAK-779. In vivo, TAK-779 significantly blocked the accumulation of renal MC in MRL/lpr mice. Our study indicate that the chemokine receptors CCR5 and CXCR4 and the integrin alpha E are important mediators of renal MC recruitment.