Immunohistochemical observations on the kinetics of macrophages and myofibroblasts in rat renal interstitial fibrosis induced by cis-diamminedichloroplatinum

Yamate, Jyoji; Tatsumi, Masashi; Nakatsuji, Shunji; Kuwamura, Mitsuru; Kotani, Takao; Sakuma, Shinya

doi:10.1016/s0021-9975(05)80087-8

Cited by 52 publications

(65 citation statements)

References 10 publications

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“…The cells are characterized by the presence of cytoplasmic myofilaments immunopositive for SMA (5,8,10,22,26,30,39). As described in obstructed rabbit kidneys (21) and cisplatin-induced rat renal fibrosis (39,43), we also confirmed by electron microscopy the presence of myofibroblasts with cytoplasmic actinlike microfilaments in rat fibrotic lesions.…”

Section: Tgf-f3 Immunostainingsupporting

confidence: 79%

“…Such a preferential arrangement has not been described in previous studies of obstructed kidneys (5,21,35) and of chemically induced renal fibrosis (4,6,28,39,43,45). In experimental dermal wound healing in mice, myofibroblasts align circumferentially to the wound margin to close the wound in a purse-string effect ( 1 ).…”

Section: Tgf-f3 Immunostainingmentioning

confidence: 75%

“…The fine structures closely resembled those reported previously in obstructed rabbit kidneys (21). These cells were regarded as myofibroblasts (21,39,43 small number of EDl-positive cells were detected in the medulla and papilla of the obstructed kidneys (Fig. 10).…”

Section: Sma-positive Cellsmentioning

confidence: 99%

“…T lymphocytes can release lymphokines that modulate the production/accumulation of ECM (19). Macrophage influx has also been observed in chemically induced or immune-mediated renal lesions (4,6,19,28,31,39,43,45); thus, special attention is focused on the relationship between macrophage influx and myofibroblast involvement.…”

Section: Tgf-f3 Immunostainingmentioning

confidence: 99%

“…The fibrotic lesion is evoked through complex pathologic processes, requiring participation of various inflammatory cells and abnormal accumulation of extracellular matrices (ECM) (5,7,9,19,35,39). To clarify the pathogenesis, nephrotoxic chemicals such as puromycin aminonucleoside (4,6,7), adriamycin (28), cyclosporine (45), and cisdiamminedichloroplatinum (cisplatin) (39,43) have been used to chemically induce renal interstitial fibrosis in rats.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Tgf-f3 Immunostainingsupporting

confidence: 79%

Section: Tgf-f3 Immunostainingmentioning

confidence: 75%

Section: Sma-positive Cellsmentioning

confidence: 99%

Section: Tgf-f3 Immunostainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Morphology of interstitial cells in the healthy kidney

et al. 1996

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Renal interstitial cells play an important role in renal function and renal diseases. We describe the morphology of renal interstitial cells in the healthy kidney. We distinguish within the renal interstitium (1) renal fibroblasts and (2) cells of the immune system. Fibroblasts are in the majority and constitute the scaffold of the kidney; they are interconnected by junctions, and are attached to tubules and vessels. Although the phenotype of fibroblasts shows some variation depending on their location in the kidney and on their functional stage, their recognition as fibroblasts is possible on account of structural features. Among the cell types of the second group, antigen-presenting dendritic cells are the most abundant in in the peritubular interstitial spaces of healthy kidneys. Their incidence is highest in the inner stripe of the outer medulla. They share some morphological features with fibroblasts but lack others--junctional complexes, morphologically defined connections with tubules and vessels, and the prominent layer of actin filaments under the plasma membrane--that are characteristic for fibroblasts. Dendritic cells in healthy kidneys are morphologically different from macrophages, which are characterized by abundant primary and secondary lysosomes. In healthy kidneys macrophages are restricted to the connective tissue of the renal capsule and the pelvic wall, and to the periarterial connective tissue. Lymphocytes are rare in healthy kidneys. The distinction of cell types by morphology is supported by differences of membrane proteins. Among all interstitial cells in the renal cortex, fibroblasts alone exhibit ecto-5'-nucleotidase. Dendritic cells constitutively have a high abundance of MHC class II protein. Both proteins are mutually exclusive. Rat macrophages display the membrane antigen ED 2 and lymphocytes exhibit specific surface antigens, depending on their type and functional stage, e.g., CD4 or CD8.

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Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin

Sato

Yamate

Saito

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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This study was undertaken to investigate the effect of taurine on the infiltration of macrophages and the progression of renal interstitial fibrosis in the kidneys of rats treated with cisplatin (CDDP). Male rats in different groups were treated as follows: (1) saline as control, (2) CDDP and (3) CDDP plus taurine in drinking water. At weeks 2, 4 and 6 after the fifth CDDP injection, we examined platinum content, the kinetics of macrophages and the areas of fibrosis. In the histologic analyses, fibrotic areas were found to have developed around dilated or atrophic tubules in the corticomedullary junction in the kidneys of CDDP-treated rats, while CDDP-plus-taurine-treated rats showed a reduction of the extent and magnitude of damage. These findings reflect the fact that the percentage of fibrotic areas in the kidney of CDDP-plus-taurine-treated rats was significantly lower than in that of CDDP-injected rats throughout the recovery period ( P<0.05). Compared with normal rats, the macrophages in CDDP-injected rats showed significant increases in number at weeks 2, 4 and 6 ( P<0.05). In contrast, the number of macrophages in CDDP-plus-taurine-treated rats was significantly smaller than that of CDDP-injected rats. These results suggested that taurine suppressed the increase of infiltrating macrophages, and led to the attenuation of renal interstitial fibrosis ( P<0.05).

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Immunohistochemical observations on the kinetics of macrophages and myofibroblasts in rat renal interstitial fibrosis induced by cis-diamminedichloroplatinum

Cited by 52 publications

References 10 publications

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

Morphology of interstitial cells in the healthy kidney

Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin

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