Immunological aspects of acute ureteral obstruction: Immune cell infiltrate in the kidney

Schreiner, George F.; Harris, Kevin; Purkerson, Mabel L.; Klahr, Saulo

doi:10.1038/ki.1988.207

Cited by 234 publications

(120 citation statements)

References 12 publications

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“…In both disease models the number of infiltrating macrophages and T cells was strongly reduced by Fab A77 treatment. Most leukocytes found in diseased kidneys are recruited from the circulation (43,44). In the UUO model, we showed by means of adoptive transfer experiments with Fc␣RI transgenic macrophages that Fab A77 treatment directly inhibited the influx of these cells.…”

Section: Discussionmentioning

confidence: 95%

Inhibitory ITAM Signaling by FcαRI-FcRγ Chain Controls Multiple Activating Responses and Prevents Renal Inflammation

Kanamaru

Pfirsch

Aloulou

et al. 2008

The Journal of Immunology

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Inhibitory signaling is an emerging function of ITAM-bearing immunoreceptors in the maintenance of homeostasis. Monovalent targeting of the IgA Fc receptor (FcαRI or CD89) by anti-FcαRI Fab triggers potent inhibitory ITAM (ITAMi) signaling through the associated FcRγ chain (FcαRI-FcRγ ITAMi) that prevents IgG phagocytosis and IgE-mediated asthma. It is not known whether FcαRI-FcRγ ITAMi signaling controls receptors that do not function through an ITAM and whether this inhibition requires Src homology protein 1 phosphatase. We show in this study that FcαRI-Fcγ ITAMi signals depend on Src homology protein 1 phosphatase to target multiple non-ITAM-bearing receptors such as chemotactic receptors, cytokine receptors, and TLRs. We found that anti-FcαRI Fab treatment in vivo reduced kidney inflammation in models of immune-mediated glomerulonephritis and nonimmune obstructive nephropathy by a mechanism that involved decreased inflammatory cell infiltration and fibrosis development. This treatment also prevented ex vivo LPS activation of monocytes from patients with lupus nephritis or vasculitis, as well as receptor activation through serum IgA complexes from IgA nephropathy patients. These findings point to a crucial role of FcαRI-FcRγ ITAMi signaling in the control of multiple heterologous or autologous inflammatory responses. They also identify anti-FcαRI Fab as a new potential therapeutic tool for preventing progression of renal inflammatory diseases.

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Section: Discussionmentioning

confidence: 95%

Inhibitory ITAM Signaling by FcαRI-FcRγ Chain Controls Multiple Activating Responses and Prevents Renal Inflammation

Kanamaru

Pfirsch

Aloulou

et al. 2008

The Journal of Immunology

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“…[23][24][25] Earlier studies have shown that macrophage/monocyte infiltration occurred in the kidney 4 h after acute ureteral obstruction and its peak response occurred at 24 h after UUO and stabilized thereafter. 26 Another study also showed a highly significant correlation between the increasing number of interstitial macrophage/monocyte and the cortical TGF-b mRNA levels. 27 Taken together, these results suggest that macrophage/monocyte is one potential source for the increased gene expression of TGF-b.…”

Section: Discussionmentioning

confidence: 97%

Beneficial effects of a combination of Rho-kinase inhibitor and ACE inhibitor on tubulointerstitial fibrosis induced by unilateral ureteral obstruction

et al. 2010

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We and others recently reported that long-term Rho-kinase inhibition has renoprotective effects. This study was designed to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (imidapril), a Rho-kinase inhibitor (fasudil) and a combination of them both on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the mechanism involved. Imidapril (50 mg l -1 ), fasudil (1 g l -1 ) or a combination of them both was given in drinking water to mice, and their effects were compared on renal interstitial fibrosis induced by UUO. We assessed histological findings, monocyte/macrophage infiltration, myofibroblast differentiation, oxidative stress and the expression of various mRNA in the kidney by UUO. Eleven days after UUO, wild-type kidney was characterized by increased fibrotic area, dihydroethidium (DHE)-positive area, a-smooth muscle actin (SMA)-positive area, F4/80-positive area and the increased expression of various mRNA. Fasudil and imidapril similarly improved fibrotic area (À23%, À15%), DHE-positive area (À13%, À11%), a-SMA-positive area (À22%, À15%), F4/80-positive area (À42%, À34%) and the expression of various mRNA, most of which were significant (Po0.05). The combination of imidapril and fasudil further improved fibrotic area (À52%), DHE-positive area (À26%), a-SMApositive area (À33%), F4/80-positive area (À62%) and the expression of various mRNA (all Po0.05 vs. monotherapy). Compared with either agent alone, the combination of an ACE inhibitor and a Rho-kinase inhibitor was more effective for the prevention of renal interstitial fibrosis because of the inhibition of transforming growth factor-b/collagen, monocyte/macrophage infiltration, myofibroblast differentiation, inflammation and the oxidative stress pathway.

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“…14) (5,20,21,27,33,35). Gradual dilation of renal tubules and flattening of epithelial cells were also observed in the present study.…”

Section: Tgf-f3 Immunostainingmentioning

confidence: 99%

“…Many investigators have reported reactive cells involved in an early phase of obstruction in the kidneys of rats and rabbits (3, 5, 15,20,27,33); increased numbers of macrophages, T lymphocytes, and myofibroblasts have been observed. However, the appearance of macrophages and myofibroblasts during chronic phases of fibrosis caused by long-term ureteral obstruction has not been described in detail.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Analysis of Macrophages, Myofibroblasts, and Transforming Growth Factor-β Localization during Rat Renal Interstitial Fibrosis Following Long-Term Unilateral Ureteral Obstruction

et al. 1998

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Renal interstitial fibrosis was induced in rats by chronic unilateral ureteral obstruction (UUO). To identify the mechanisms behind the fibrosis, macrophage influx, myofibroblast involvement, and the localization of transforming growth factor-β (TGF-β, a fibrogenic cytokine) were investigated immunohistochemically in rats euthanatized at 0 (controls), 3,6,9,12, and 15 days after UUO. The number of α-smooth muscle actin-positive myofibroblasts began to increase significantly in the medulla from day 3, and the development of medullary fibrosis was confirmed from day 6 by morphometric analysis. From day 9, papillary fibrosis also developed in association with an increased number of myofibroblasts. These myofibroblasts showed a parallel orientation to the mucosal surface of the pelvis. In the medulla and papilla, from day 6 the number of ED1 (primary antibody)-positive macrophages began to increase significantly. There appeared to be a relationship between macrophage influx and myofibroblast involvement. By contrast, in the cortex there was no marked increase in myofibroblasts nor development of fibrotic tissues, regardless of increased number of macrophages from day 6. Immunohistochemically, no staining for TGF-β was found in infiltrating macrophages or myofibroblasts. However, TGF-& b e t a ; was localized on some cortical proximal renal tubules both of normal control and obstructed kidneys in the early stages on days 3, 6, and 9, suggesting that the possible origin of TGF-β may be renal epithelia. However, the staining intensity for TGF-β on the renal epithelia tended to be weakened in advanced obstructed kidneys on days 12 and 15. The likely contribution of TGF-β to the advanced stages of UUO-induced renal fibrosis remains to be determined.

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Immunological aspects of acute ureteral obstruction: Immune cell infiltrate in the kidney

Cited by 234 publications

References 12 publications

Inhibitory ITAM Signaling by FcαRI-FcRγ Chain Controls Multiple Activating Responses and Prevents Renal Inflammation

Inhibitory ITAM Signaling by FcαRI-FcRγ Chain Controls Multiple Activating Responses and Prevents Renal Inflammation

Beneficial effects of a combination of Rho-kinase inhibitor and ACE inhibitor on tubulointerstitial fibrosis induced by unilateral ureteral obstruction

Immunohistochemical Analysis of Macrophages, Myofibroblasts, and Transforming Growth Factor-β Localization during Rat Renal Interstitial Fibrosis Following Long-Term Unilateral Ureteral Obstruction

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