Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis.
BACKGROUND
We established the reversible and the prolonged models of mesangial proliferative glomerulonephritis (GN) with anti-Thy 1 antibody 1-22-3. However, the essential factors leading to the prolonged glomerular alterations have not been identified.


METHODS
The expressions of several chemokines and cytokines were compared in the reversible and the prolonged models. Expression of fractalkine and the number of the fractalkine receptor CX3CR1-positive cells in the glomeruli in the prolonged model were significantly higher than those in the reversible model. Then, the localization of fractalkine and the characteristics of CX3CR1+ cells were analyzed in glomeruli. To elucidate the significance of the fractalkine expression, we analyzed the expression in the model treated with angiotensin II receptor antagonist, candesartan.


RESULTS
Immunostaining of fractalkine was detected on endothelial cells on the fifth day, and fractalkine staining also was detected in the mesangial area on day 14. Major parts of the CX3CR1+ cells in the glomeruli were macrophages, especially ED3+ cells. Candesartan treatment ameliorated the glomerular morphological findings at six weeks after disease induction. Although the treatment did not ameliorate the morphological finding at two weeks, decreased expression of fractalkine and CX3CR1+ were already detected at two weeks in rats treated with candesartan.


CONCLUSIONS
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.
Ito
Yumi
Y
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Kawachi
Hiroshi
H
Morioka
Yoshio
Y
Nakatsue
Takeshi
T
Koike
Hiroko
H
Ikezumi
Yohei
Y
Oyanagi
Akihisa
A
Natori
Yasuhiro
Y
Natori
Yumiko
Y
Nakamura
Takamichi
T
Gejyo
Fumitake
F
Shimizu
Fujio
F
D000818:Animals; D000911:Antibodies, Monoclonal; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D018925:Chemokines / Q000235:genetics; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D002908:Chronic Disease; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009392:Nephrectomy / Q000379:methods; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D018925:Chemokines; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D013777:Tetrazoles; C081643:candesartan