PMID- 19737241 OWN - NLM STAT- MEDLINE VI - 158 IP - 1 TI - Spatiotemporal expression of chemokines and chemokine receptors in experimental anti-myeloperoxidase antibody-mediated glomerulonephritis. PG - 143-53 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 IS - 1365-2249 (Electronic) LID - 10.1111/j.1365-2249.2009.03993.x [doi] FAU - van der Veen, B S AU - van der Veen BS AD - Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. FAU - Petersen, A H AU - Petersen AH FAU - Belperio, J A AU - Belperio JA FAU - Satchell, S C AU - Satchell SC FAU - Mathieson, P W AU - Mathieson PW FAU - Molema, G AU - Molema G FAU - Heeringa, P AU - Heeringa P IS - 0009-9104 (Linking) RN - 0 (Antibodies, Antineutrophil Cytoplasmic) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokine CXCL2) RN - 0 (Chemokine CXCL5) RN - 0 (Chemokines) RN - 0 (Immune Sera) RN - 0 (Immunoglobulin G) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Interleukin-8B) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Animals MH - Antibodies, Antineutrophil Cytoplasmic/immunology MH - Chemokine CXCL1/genetics MH - Chemokine CXCL2/genetics MH - Chemokine CXCL5/genetics MH - Chemokines/*genetics MH - Endothelial Cells/immunology/metabolism MH - Female MH - Gene Expression MH - *Gene Expression Regulation MH - Glomerulonephritis/*immunology/metabolism MH - Immune Sera/pharmacology MH - Immunoglobulin G/pharmacology MH - Kidney Glomerulus/*immunology/metabolism MH - Kidney Tubules/immunology/metabolism MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Models, Animal MH - Neutrophils/immunology/metabolism MH - Peroxidase/immunology MH - Receptors, Chemokine/*genetics MH - Receptors, Interleukin-8B/immunology MH - Time Factors PMC - PMC2759069 DCOM- 20091009 LR - 20211020 DP - 2009 Oct AB - Myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing crescentic glomerulonephritis (NCGN) is characterized by abundant leucocyte infiltration. Chemokines are chemotactic cytokines involved in receptor-mediated recruitment of leucocytes. Our objective was to analyse spatiotemporal gene expression of chemokines and chemokine receptors in anti-MPO-mediated NCGN, to find potential targets for intervening with leucocyte influx. NCGN was induced in mice by co-administration of anti-MPO immunoglobulin (Ig)G and lipopolysaccharide. mRNA expression levels of chemokines and chemokine receptors were analysed in whole kidney lysates as well as in laser microdissected glomeruli and tubulo-interstitial tissue 1 and 7 day(s) after NCGN induction. Several chemokines and chemokine receptors were induced or up-regulated in anti-MPO-mediated NCGN, both on day 1 (chemokines CCL3, 5; CXCL2, 5, 13; receptor CXCR2) and on day 7 (chemokines CCL2, 5, 7, 8, 17, 20; CXCL1, 2, 5, 10; CX(3)CL1; receptors CCR2, 8; CX(3)CR1). The expression levels of most chemokines and receptors were higher in glomeruli than in the tubulo-interstitium. Because of the temporal induction of CXCR2 on day 1, we hypothesized CXCR2 as a potential target for treatment in anti-MPO-induced NCGN. Inhibition of CXCR2 using a goat-anti-CXCR2 serum prior to NCGN induction increased glomerular neutrophil influx but did not affect crescent formation and albuminuria. In conclusion, expression levels of various chemokines and chemokine receptors were increased in anti-MPO NCGN, and expressed particularly in glomeruli. These chemokines and receptors may serve as potential targets for treatment. Inhibition of a single target, CXCR2, did not attenuate anti-MPO NCGN. Combinatorial interventions may be necessary to avoid redundancy.