Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis

Ito, Yumi; Kawachi, Hiroshi; Morioka, Yuhei; T, Nakatsue; Koike, Hiroko; Ikezumi, Yohei; Oyanagi, Akihisa; Natori, Yasuhiro; Natori, Yumiko; Nakamura, Takamichi; Gejyo, Fumitake; Shimizu, Fujio

doi:10.1046/j.1523-1755.2002.00369.x

Cited by 47 publications

(38 citation statements)

References 40 publications

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“…In the kidney, an important role for CX 3 CL1 has been found in diseases that involve glomerular inflammation and endothelial injury (19,20,22,23). CX 3 CL1 also is upregulated in renal tubulointerstitial inflammation, most notably in acute allograft rejection (19), but the specific localization of the chemokine (apical versus basolateral) has been somewhat unclear (32).…”

Section: Discussionmentioning

confidence: 99%

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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The chemokine CX 3 CL1 plays a key role in glomerulonephritis and can act as both chemoattractant and adhesion molecule. CX 3 CL1 also is upregulated in tubulointerstitial injury, but little is known about the subcellular distribution and function of CX 3 CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it was found that CX 3 CL1 is expressed predominantly on the apical surface of tubular epithelium in human renal transplant biopsy specimens with acute rejection or acute tubular necrosis. For studying the targeting of CX 3 CL1 in polarized RTEC, MDCK cells that expressed untagged or green fluorescent protein-tagged CX 3 CL1 were generated. The chemokine was present on the apical membrane and in subapical vesicles. Apical targeting of CX 3 CL1 was not due to signals that were conferred by its intracellular domain, to associations with lipid rafts, or to O-glycosylation but, rather, depended on N-linked glycosylation of the protein. With the use of fluorescence recovery after photobleaching, it was found that CX 3 CL1 is immobile in the apical membrane. However, CX 3 CL1 partitioned with the triton-soluble rather than -insoluble cellular fraction, indicating that it is not associated directly with the actin cytoskeleton or with lipid rafts. Accordingly, disruption of rafts through cholesterol depletion did not render CX 3 CL1 mobile. For exploration of potential functions of apical CX 3 CL1, binding of CX 3 CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte adhesion to the luminal surface was enhanced significantly when CX 3 CL1 was present. These data demonstrate that CX 3 CL1 is expressed preferentially on the apical membrane of RTEC and suggest a novel function for the chemokine in recruitment and retention of leukocytes in tubulointerstitial inflammation.

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Section: Discussionmentioning

confidence: 99%

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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“…The severity of morphologic alterations was evaluated in a double-blind manner with Ͼ30 full-sized glomeruli (80 to 100 m) from each specimen. The severity of mesangiolysis, mesangial matrix expansion, and the intensity of ␣-SMA staining were scored as described previously by Ito et al (21). To analyze whether inflammatory responses are affected by the anti-IP-10 mAb treatment, we counted the number of OX-1-, ED1-, and OX-19 -positive inflammatory cells in glomeruli.…”

Section: Experimental Designmentioning

confidence: 99%

“…Tissue samples for LM assessment and for the IF studies were prepared as described previously (21). The 3-m-thick frozen sections were cut with a cryostat and stained with goat anti-IP-10 antibody (Santa Cruz Biotechnology), goat anti-CXCR3 antibody (Santa Cruz Biotechnology), rabbit anti-nephrin antibody (intracellular site) (26), rabbit anti-podocin antibody (N-terminal site) (27), and rabbit antipodoplanin antibody (28).…”

Section: Morphologic and Immunohistochemical Studiesmentioning

confidence: 99%

“…Semiquantitative RT-PCR with glomerular RNA was performed basically according to the method described previously (21). The primers were designed according to the published sequences (Table 1).…”

Section: Rt-pcrmentioning

confidence: 99%

“…Mesangial proliferative glomerulonephritis (GN) including IgA nephropathy is one of the most important diseases in the nephrology field. Anti-Thy1.1 antibody-induced GN (Thy1.1 GN) is most commonly used as a model of mesangial proliferative GN (21). However, no precise studies of the role of IP-10 on the pathogenesis of Thy1.1 GN are reported.…”

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confidence: 99%

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IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

Han¹,

Koike²,

Nakatsue³

et al. 2003

Journal of the American Society of Nephrology

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Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice

Inoue¹,

Hasegawa²,

Kohno³

et al. 2005

Arthritis & Rheumatism

122

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Objective. Lupus nephritis is characterized by immune complex deposition and inflammatory cell infiltration into the renal glomeruli. Local generation of chemokines and the presence of chemokine receptors on the infiltrating cells may be involved in this process. Fractalkine (Fkn)/CX3CL1 and its receptor, CX3CR1, form one such chemokine system. We therefore undertook this study to investigate whether Fkn antagonist inhibits the initiation and progression of lupus nephritis in MRL/lpr mice.Methods. NH 2 -terminally truncated Fkn/CX3CL1 analogs were transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, and injected subcutaneously into MRL/lpr mice.Results. Fkn analogs truncated by >4 amino acid residues from the N-terminus failed to induce chemotaxis and calcium influx by CX3CR1-expressing cells. Of these, the most potent antagonist (Fkn-AT) lacked the 4 N-terminal amino acid residues. Fkn expression in the glomerulus was significantly increased in 12-weekold MRL/lpr mice. Expression was localized predominantly in the glomerular endothelial cells, but was occasionally observed in the mesangial cells and, to a lesser extent, in the interstitial microvasculature. Inoculation of MRL/lpr mice with Fkn-AT before the onset or during the early stages of lupus nephritis significantly reduced glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to a marked reduction in macrophage accumulation. In contrast, Fkn antagonist did not affect pneumonitis, sialadenitis, lymphadenopathy, or splenomegaly.Conclusion. We prepared a novel potent Fkn antagonist and demonstrated its ability to delay the initiation and ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach to lupus nephritis.

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Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis

Abstract: Fractalkine expression and the recruitment of CX3CR1+ cells in glomeruli might play an important role in the development of the prolonged disease. These expressions could be predictors of the prolonged disease of the mesangial proliferative glomerulonephritis.

Cited by 47 publications

References 40 publications

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

IFN-Inducible Protein-10 Has a Differential Role in Podocyte during Thy 1.1 Glomerulonephritis

Antagonist of fractalkine (CX3CL1) delays the initiation and ameliorates the progression of lupus nephritis in MRL/lpr mice

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