Abstract
In this chapter we present methods for the isolation and characterization of mononuclear phagocytes from the kidneys of mice with SLE. Activation of these cells is associated with the onset of clinical disease in mice and infiltration with these cells is associated with poor prognosis in humans. Using magnetic beads followed by flow cytometric sorting, pure populations of cells are obtained that are functional in a variety of assays. Sufficient numbers of cells are obtained for genomic characterization. An analysis of the function of these cells should lead to a better understanding of the inflammatory processes that cause renal impairment in SLE and other renal inflammatory diseases.
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References
Davidson A, Aranow C (2006) Pathogenesis and treatment of systemic lupus erythematosus nephritis. Curr Opin Rheumatol 18:468–475
Chan TM (2005) Preventing renal failure in patients with severe lupus nephritis. Kidney Int Suppl 94:S116–S119
Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980
Contreras G, Tozman E, Nahar N, Metz D (2005) Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil, azathioprine and intravenous cyclophosphamide. Lupus 14(Suppl 1):s33–s38
Costenbader KH, Solomon DH, Winkelmayer W, Brookhart MA (2008) Incidence of end-stage renal disease due to lupus nephritis in the U.S., 1995–2004. Arthrit Rheum Abstract 1927
Schwartz MM (2007) The pathology of lupus nephritis. Semin Nephrol 27:22–34
Hill GS, Delahousse M, Nochy D, Mandet C, Bariety J (2001) Proteinuria and tubulointerstitial lesions in lupus nephritis. Kidney Int 60:1893–1903
Hill GS, Delahousse M, Nochy D, Remy P, Mignon F, Mery JP, Bariety J (2001) Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages. Kidney Int 59:304–316
Li QZ, Xie C, Wu T, Mackay M, Aranow C, Putterman C, Mohan C (2005) Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays. J Clin Invest 115:3428–3439
Bagavant H, Fu SM (2005) New insights from murine lupus: disassociation of autoimmunity and end organ damage and the role of T cells. Curr Opin Rheumatol 17:523–528
Christensen SR, Kashgarian M, Alexopoulou L, Flavell RA, Akira S, Shlomchik MJ (2005) Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J Exp Med 202:321–331
Turnberg D, Cook HT (2005) Complement and glomerulonephritis: new insights. Curr Opin Nephrol Hypertens 14:223–228
Clynes R, Dumitru C, Ravetch JV (1998) Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science 279:1052–1054
Anders HJ, Schlondorff D (2007) Toll-like receptors: emerging concepts in kidney disease. Curr Opin Nephrol Hypertens 16:177–183
Sesin CA, Yin X, Esmon CT, Buyon JP, Clancy RM (2005) Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: in vivo and in vitro evidence. Kidney Int 68:110–120
Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ (1999) A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med 189:1639–1648
Lewis EJ, Schwartz MM (2005) Pathology of lupus nephritis. Lupus 14:31–38
Anders HJ, Ninichuk V, Schlondorff D (2006) Progression of kidney disease: blocking leukocyte recruitment with chemokine receptor CCR1 antagonists. Kidney Int 69:29–32
Holdsworth SR, Tipping PG (2007) Leukocytes in glomerular injury. Semin Immunopathol 29:355–374
Foster MH (2007) T cells and B cells in lupus nephritis. Semin Nephrol 27:47–58
Schiffer L, Sinha J, Wang X, Huang W, von Gersdorff G, Schiffer M, Madaio MP, Davidson A (2003) Short term administration of costimulatory blockade and cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F1 mice by a mechanism downstream of renal immune complex deposition. J Immunol 171:489–497
Daikh DI, Wofsy D (2001) Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol 166:2913–2916
Timoshanko JR, Sedgwick JD, Holdsworth SR, Tipping PG (2003) Intrinsic renal cells are the major source of tumor necrosis factor contributing to renal injury in murine crescentic glomerulonephritis. J Am Soc Nephrol 14:1785–1793
Wang Y, Wang Y, Cai Q, Zheng G, Lee VW, Zheng D, Li X, Tan TK, Harris DC (2008) By homing to the kidney, activated macrophages potently exacerbate renal injury. Am J Pathol 172:1491–1499
Ferenbach D, Hughes J (2008) Macrophages and dendritic cells: what is the difference? Kidney Int 74:5–7
Kurts C, Heymann F, Lukacs-Kornek V, Boor P, Floege J (2007) Role of T cells and dendritic cells in glomerular immunopathology. Semin Immunopathol 29:317–335
Mosser DM (2003) The many faces of macrophage activation. J Leukoc Biol 73:209–212
Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969
Hume DA (2008) Differentiation and heterogeneity in the mononuclear phagocyte system. Mucosal Immunol 1:432–441
Tacke F, Randolph GJ (2006) Migratory fate and differentiation of blood monocyte subsets. Immunobiology 211:609–618
Li L, Huang L, Sung SS, Vergis AL, Rosin DL, Rose CE Jr, Lobo PI, Okusa MD (2008) The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury. Kidney Int 74:1526–1537
Swaminathan S, Griffin MD (2008) First responders: understanding monocyte-lineage traffic in the acutely injured kidney. Kidney Int 74:1509–1511
Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666–670
Geissmann F, Auffray C, Palframan R, Wirrig C, Ciocca A, Campisi L, Narni-Mancinelli E, Lauvau G (2008) Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses. Immunol Cell Biol 86:398–408
Skold M, Behar SM (2008) Tuberculosis triggers a tissue-dependent program of differentiation and acquisition of effector functions by circulating monocytes. J Immunol 181:6349–6360
Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461
Wu L, Liu YJ (2007) Development of dendritic-cell lineages. Immunity 26:741–750
Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat Immunol 8:578–583
Auffray C, Emre Y, Geissmann F (2008) Homeostasis of dendritic cell pool in lymphoid organs. Nat Immunol 9:584–586
Kamath AT, Henri S, Battye F, Tough DF, Shortman K (2002) Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100:1734–1741
Kruger T, Benke D, Eitner F, Lang A, Wirtz M, Hamilton-Williams EE, Engel D, Giese B, Muller-Newen G, Floege J, Kurts C (2004) Identification and functional characterization of dendritic cells in the healthy murine kidney and in experimental glomerulonephritis. J Am Soc Nephrol 15:613–621
Soos TJ, Sims TN, Barisoni L, Lin K, Littman DR, Dustin ML, Nelson PJ (2006) CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney. Kidney Int 70:591–596
Segerer S, Heller F, Lindenmeyer MT, Schmid H, Cohen CD, Draganovici D, Mandelbaum J, Nelson PJ, Grone HJ, Grone EF, Figel AM, Nossner E, Schlondorff D (2008) Compartment specific expression of dendritic cell markers in human glomerulonephritis. Kidney Int 74:37–46
Kurts C (2006) Dendritic cells: not just another cell type in the kidney, but a complex immune sentinel network. Kidney Int 70:412–414
Bethunaickan R, Berthier CC, Ramanujam M, Sahu R, Zhang W, Sun Y, Bottinger EP, Ivashkiv L, Kretzler M, Davidson A (2011) A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis. J Immunol:186:4994–5003
Ramanujam M, Davidson A (2008) Targeting of the immune system in systemic lupus erythematosus. Expert Rev Mol Med 10:e2
Singh RR, Saxena V, Zang S, Li L, Finkelman FD, Witte DP, Jacob CO (2003) Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis. J Immunol 170:4818–4825
Santiago ML, Fossati L, Jacquet C, Muller W, Izui S, Reininger L (1997) Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome. J Exp Med 185:65–70
Matsumoto K, Watanabe N, Akikusa B, Kurasawa K, Matsumura R, Saito Y, Iwamoto I, Saito T (2003) Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice. Arthritis Rheum 48:486–494
Ehlers M, Fukuyama H, McGaha TL, Aderem A, Ravetch JV (2006) TLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE. J Exp Med 203:553–561
Wu X, Peng SL (2006) Toll-like receptor 9 signaling protects against murine lupus. Arthritis Rheum 54:336–342
Fu Y, Du Y, Mohan C (2007) Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis. Clin Immunol 124:109–118
Perry D, Sang A, Yin Y, Zheng YY, Morel L (2011) Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011:271694
Ramanujam M, Wang X, Huang W, Liu Z, Schiffer L, Tao H, Frank D, Rice J, Diamond B, Yu KO, Porcelli S, Davidson A (2006) Similarities and differences between selective and nonselective BAFF blockade in murine SLE. J Clin Invest 116:724–734
Rudofsky UH, Lawrence DA (1999) New Zealand mixed mice: a genetic systemic lupus erythematosus model for assessing environmental effects. Environ Health Perspect 107:713–721
Ramanujam M, Davidson A (2008) BAFF blockade for systemic lupus erythematosus – will the promise be fulfilled? Immunol Rev 223:156–174
Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S (2006) Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312:1669–1672
Subramanian S, Tus K, Li QZ, Wang A, Tian XH, Zhou J, Liang C, Bartov G, McDaniel LD, Zhou XJ, Schultz RA, Wakeland EK (2006) A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci USA 103:9970–9975
Haywood ME, Rogers NJ, Rose SJ, Boyle J, McDermott A, Rankin JM, Thiruudaian V, Lewis MR, Fossati-Jimack L, Izui S, Walport MJ, Morley BJ (2004) Dissection of BXSB lupus phenotype using mice congenic for chromosome 1 demonstrates that separate intervals direct different aspects of disease. J Immunol 173:4277–4285
Akkerman A, Huang W, Wang X, Ramanujam M, Schiffer L, Madaio M, Factor SM, Davidson A (2004) CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice. Autoimmunity 37:445–451
Kahn P, Ramanujam M, Bethunaickan R, Huang W, Tao H, Madaio MP, Factor SM, Davidson A (2008) Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum 58:2824–2834
Hang LM, Izui S, Dixon FJ (1981) (NZW × BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction. J Exp Med 154:216–221
Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317
Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Dixon FJ (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148:1198–1215
Menke J, Rabacal WA, Byrne KT, Iwata Y, Schwartz MM, Stanley ER, Schwarting A, Kelley VR (2009) Circulating CSF-1 promotes monocyte and macrophage phenotypes that enhance lupus nephritis. J Am Soc Nephrol 20:2581–2592
Hoi AY, Hickey MJ, Hall P, Yamana J, O’Sullivan KM, Santos LL, James WG, Kitching AR, Morand EF (2006) Macrophage migration inhibitory factor deficiency attenuates macrophage recruitment, glomerulonephritis, and lethality in MRL/lpr mice. J Immunol 177:5687–5696
Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MP, Bottinger EP, Davidson A (2008) Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis. J Immunol 180:1938–1947
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Bethunaickan, R., Sahu, R., Davidson, A. (2012). Analysis of Renal Mononuclear Phagocytes in Murine Models of SLE. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_10
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DOI: https://doi.org/10.1007/978-1-60761-720-4_10
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