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1.
Chen CA Hwang JC Guh JY Chang JM Lai YH Chen HC 《The Journal of laboratory and clinical medicine》2006,147(2):74-82
Integrins attach cells to extracellular matrix (ECM) and mediate signals from ECM to cells or from cells to ECM. They regulate cell functions, including adhesion, migration, cell cycle regulation, and differentiation. Podocytes may detach from the glomerular basement membrane (GBM) and be excreted in the urine, and proteinuria is found in patients with primary focal segmental glomerulosclerosis (FSGS); both may be associated with loss of alpha3beta1integrins. In this study, we have examined the podocyte number in patients with primary FSGS and normal controls, and the alpha3- and beta1-integrin subunits expression of podocytes in patients with primary FSGS and chronic puromycin aminonucleoside (PAN)-treated rats by the morphometric, immunoperoxidase histochemical, and immunoelectron microscopic examination. We also measured their expression serially in rats that received repeated PAN injection. The results showed that the podocyte number was significantly decreased in patients with primary FSGS than in normal control (P < 0.05). The immunostaining score showed that both alpha3- and beta1-integrin subunits on podocytes in patients with primary FSGS were significantly lower than in normal controls (both P < 0.01). The number of immuno-gold particles of alpha3- and beta1-integrins at the effaced foot process area of patients with primary FSGS were also significantly decreased than that of normal controls (both P < 0.05). The immunostaining score of both alpha3- and beta1-integrin subunits was negatively correlated with the degree of glomerular sclerosing score and the amount of daily protein loss, and they were positively correlated with the number of podocytes. Chronic 12-week PAN-treated rats showed similar findings with decreased immunostaining expression and immuno-gold particles of alpha3-integrin on podocytes than in normal control (both P < 0.05). The chronic PAN-treated rats also showed a trend toward gradually decreased immunostaining expression of alpha3-integrin subunit on podocyte during the progress from normal to FSGS state. These studies indicate that podocyte expression of alpha3- and beta1-integrin subunits is significantly reduced in humans with primary FSGS and chronic PAN-treated rats, before the morphological changes of FSGS are observed. The decreased podocyte expression of alpha3beta1 integrins is closely related with podocyte depletion, glomerular sclerosis, and daily protein loss in patients with primary FSGS. 相似文献
2.
H Trachtman S Futterweit P C Singhal N Franki M Sharma R Sharma V Savin 《Journal of investigative medicine》1999,47(3):114-120
BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) recurs in nearly 30% of patients who progress to end-stage renal disease and then receive a kidney transplant. A circulating plasma factor has been isolated from these patients that increases glomerular permeability to albumin in vitro. Because of the pivotal role of the mesangial cell in the accumulation of extracellular matrix (ECM) material within the glomerulus and the modulation of matrix protein synthesis by nitric oxide (NO), we examined the effect of the FSGS factor on inducible nitric oxide synthase (iNOS) expression and NO production by cultured rat mesangial cells (RMC). METHODS: RMC were incubated with the supernatant following 70% ammonium sulfate precipitation of serum from patients with recurrent FSGS. RESULTS: Addition of the FSGS factor to cultured RMC led to a significant inhibition of nitrite accumulation, an index of NO synthesis. There was a parallel decline in iNOS gene and protein expression. Sera obtained from control patients or those with minimal change nephrotic syndrome or diabetic nephropathy that was processed in the same manner as FSGS samples had no effect NO synthesis or iNOS activity. The inhibitory effect of the FSGS factor on NO production persisted despite addition of indomethacin (0.1-1 mumol/L) or cyclosporine (25 micrograms/mL) to test media. CONCLUSIONS: These data indicate that the FSGS factor independently alters two aspects of glomerular function--permselectivity and matrix protein synthesis--by distinct mechanisms. FSGS factor-induced disturbances in iNOS gene and protein expression and NO production by mesangial cells may antagonize the antifibrotic effect of NO within the mesangium and contribute to progressive glomerulosclerosis in patients with primary FSGS. 相似文献
3.
Chiu YW Kuo MC Kuo HT Chang JM Guh JY Lai YH Chen HC 《The Journal of laboratory and clinical medicine》2005,145(4):181-186
To investigate the status and role of glutathione peroxidase (GPX) in diabetic nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these patients and in rats with streptozotocin-induced diabetes of varying duration. Plasma GPX levels were significantly lower in DGS patients than in diabetic patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX concentrations were also significantly lower in DGS patients than in diabetic patients without nephropathy or normal controls (both P < .05). Immunostaining of glomerular GPX was significantly less in DGS patients than in normal controls (P < .05) and was negatively correlated with the glomerular sclerosis score and the index of mesangial expansion. Serial examination of glomerular GPX in diabetic rats showed that immunostaining scores for glomerular GPX in rats were significantly lower than those in normal control rats after 1 and 3 months' duration of diabetes, and staining scores were also significantly lower in rats killed after 3 months of diabetes than in those killed after 1 week. In conclusion, our study demonstrates that GPX concentrations in plasma, urine, and glomeruli are decreased in individuals with DGS and that the immunostaining of glomerular GPX decreases progressively. 相似文献
4.
In a rat model of macrophage-dependent glomerular immune injury induced by administration of antibody against the glomerular basement membrane (anti-GBM), the authors assessed the anti-proteinuric effect of Heme Oxygenase-1 (HO-1) induction. Rats received anti-GBM antibody alone, anti-GBM antibody and treatment with the HO-1 inducer, hemin, or non-immune serum (controls). Urine protein, creatinine, and nitrite/nitrate excretion were measured on days 5, 7, and 14 after administration of the anti-GBM antibody. In hemin-treated animals with anti-GBM antibody-induced immune injury, HO-1 immunolocalized in macrophages infiltrating glomeruli and in tubular epithelial cells. In these animals, proteinuria was decreased. There was also a decrease in blood urea nitrogen (BUN) levels without a change in serum creatinine or systemic blood pressure. The observations establish the anti-proteinuric effect of hemin induction. This effect could be mechanistically linked to blunting of the ability of infiltrating macrophages to cause injury or to changes in tubular handling of filtered protein. 相似文献
5.
Superoxide dismutase mimetic preserves the glomerular capillary permeability barrier to protein 总被引:2,自引:0,他引:2
Duann P Datta PK Pan C Blumberg JB Sharma M Lianos EA 《The Journal of pharmacology and experimental therapeutics》2006,316(3):1249-1254
Overproduction of superoxide (O2*) occurs in glomerular disease and may overwhelm the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury by O2* and related radical species that disrupt the glomerular capillary permeability barrier to protein. We examined the efficacy of the SOD mimetic tempol in preserving glomerular permeability to protein using 1) a rat model of glomerular immune injury induced by an antiglomerular basement membrane antibody (anti-GBM), and 2) isolated rat glomeruli in which injury was induced by the cytokine tumor necrosis factor-alpha (TNFalpha). To induce glomerular immune injury, rats received anti-GBM using a protocol that results in prominent infiltration of glomeruli by macrophages and in which macrophage-derived TNFalpha has been shown to mediate albuminuria. To increase glomerular capillary permeability to albumin (P(alb)) ex vivo, isolated glomeruli were incubated with TNFalpha at concentrations (0.5-4.0 microg/ml) known to stimulate O2* production. Increments in P(alb) were detected by measuring changes in glomerular volume in response to an applied oncotic gradient. Significant increases in the urine excretion of albumin and F(2alpha)-isoprostane were observed in rats with glomerular immune injury without a significant change in systolic blood pressure. Tempol treatment significantly reduced urine isoprostane and albumin excretion. In isolated glomeruli, TNFalpha increased P(alb) and tempol abrogated this effect, both in a dose-dependent manner. These observations indicate that SOD mimetics can preserve the glomerular permeability barrier to protein under conditions of oxidative stress from O2* production. 相似文献
6.
Chen HC Guh JY Chang JM Tsai JC Hwang SJ Lai YH 《Journal of clinical laboratory analysis》2001,15(2):59-63
The kidney is an important site of endothelin-1 (ET-1) production and is particularly susceptible to ET-1 action. Infusion of ET-1 in rats induces both functional and morphological alterations in the kidneys. Increased plasma level of ET-1 has been reported in patients with chronic renal failure. However, there are still no reports on the plasma and urinary ET-1 levels in patients with focal segmental glomerulosclerosis (FSGS). In the present study, we have measured the plasma concentration and urinary excretion rate of ET-1 in 15 patients with nephrotic syndrome due to FSGS, and observed the serial changes of plasma and urinary ET-1 in nephrotic rats with FSGS, induced by repeated injection with puromycin aminonucleoside (PAN). ET-1 was measured with radioimmunoassay. The results showed that plasma ET-1 concentration in FSGS patients was significantly higher than in normal controls (P < 0.05), and that urinary ET-1 excretion rate was also significantly higher in FSGS patients than in normal controls (P < 0.01). In FSGS patients, the plasma and urinary ET-1 was significantly correlated (P < 0.05), and the urinary ET-1 excretion rate was significantly correlated with the amount of proteinuria (P < 0.05) and the glomerular sclerosing score (P < 0.01). In the ten rats with PAN-induced FSGS, serial examination showed a significant increase in plasma ET-1 after 8 weeks of injections, while the urinary ET-1 excretion rate showed a biphasic increase that showed a peak after 4 to 6 weeks. The same changes in plasma and urinary ET-1 levels were not observed in control rats injected with normal saline at the same frequency. Our results suggest that ET-1 may be involved in the pathogenesis of FSGS in both humans and rats. 相似文献
7.
Focal segmental glomerulosclerosis (FSGS) recurs in 30% of renal allograft transplants with graft loss in half of the cases. A humoral factor may be implicated. We report on the use of therapeutic plasma exchange (TPE) in 11 patients with recurrent FSGS post transplantation. Medical records from 1989-2000 were reviewed for 11 adults transplanted for biopsy proven FSGS. Ten patients developed proteinuria (x: 6.1 g; range: 3-40 g/24 h) within 2 months of transplantation. In 1 patient, proteinuria (4 g) occurred 2 years post transplantation. Biopsy in six patients revealed early recurrent FSGS, while in five, suspected recurrence was based on clinical findings. Each patient received 5-11 TPEs (x: 6) with the COBE Spectra, daily or on alternate days with 2.5-3.5 L 5% albumin as the replacement fluid. In four, FFP was included because of coagulopathy. All received immunosuppression (IS) during and after TPE. A persistent drop in 24 h urine protein (U.P.) was observed in 10/11 patients. Seven had >70% drop in 24 h U.P. following the course of TPE, while three had a reduction of 45-50%. No change occurred in 1 patient. Follow-up (9 months-5 years) of seven patients has shown a persistent U.P. of <1 g with successful allograft survival. In these patients, TPE appeared effective in early recurrent FSGS. The decrease in U.P. may result from combined TPE and IS. Although the disease is designated in category III by the ASFA, TPE should be considered early when FSGS recurrence is established. 相似文献
8.
目的 检测CD2相关蛋白(CD2 associated protein,CD2AP)、Wilms肿瘤基因(Wilms tumor gene,WT1)在成人原发性肾病综合征不同病理类型肾小球的表达,并分析二者与临床指标(如24小时尿蛋白定量、血肌酐、肾小球硬化率)的关系.方法 80例原发肾病综合征的患者,依据病理分型分为肾小球微小病变组(MCN组)20例,IgA肾病组(IgAN组)20例,膜性肾病组(MN组)20例及局灶节段性肾小球硬化组(PSGS组)20例,另选10例正常对照组,采用免疫组织化学方法检测肾小球CD2、WT1的表达和分布情况.结果 CD2AP在肾小球和部分肾小管上皮细胞刷状缘均有表达.在正常对照组CD2AP沿毛细血管壁呈均匀、线状分布.MCN组、MN组、FSGS组CD2AP沿毛细血管壁不均匀分布,呈细颗粒状,部分毛细血管壁表达缺失;IgAN组CD2AP表达不均呈断续不等颗粒状,在病变区域表达缺失.对照组、MCN组、IgAN组、MN组、FSGS组的CD2AP表达指数分别为14.35±3.29、11.69±3.36、11.84±4.37、7.67±3.06、8.71±3.06.MN组、FSGS组与正常对照组比较显著降低(P<0.05),而MCN组、IgAN组较正常对照组差异无统计学意义.MN组、FSGS组与MCN组、IgAN组比较CD2AP的表达也有显著降低(P<0.05).WT1在肾小球内沿毛细血管壁均匀分布.MCN组、IgAN组、FSGS组WT1表达强度减弱,IgAN组病变区域部分表达缺失.时照组、MCN组、IgAN组、MN组、FSGS组的CD2AP表达指数分别为3.51±0.51、2.54±0.85、2.45±0.57、3.71±1.08、1.93±0.31.MCN组、IgAN组、FSGS组与对照组比较表达明显降低,而MN与对照组差异无统计学意义.原发性肾病综合征患者肾小球CD2AP、WT1的表达水平与24小时尿蛋白定量呈负相关(r=-0.861,-0.304,P<0.05).结论 成人原发性肾病综合征不同病理类型肾小球CD2AP、WT1的表达和分布不同,二者与24小时尿蛋白定量呈负相关. 相似文献
9.
Glutathione peroxidase (GPX) is an important antioxidant that effectively scavenges hydrogen peroxide. Recent studies have revealed that plasma GPX activity is decreased in patients with chronic kidney failure. However, there have been no reports on renal and urinary GPX levels in patients with kidney disorders. Therefore in this study we have measured the plasma and urinary GPX levels and glomerular GPX immunostaining in patients with focal segmental glomerulosclerosis (FSGS) and normal kidney function as compared with those in patients with minimal change disease (MCD) and those in normal control subjects. Rats with puromycin aminonucleoside-induced FSGS were also studied. The results showed that the plasma GPX level was significantly lower in FSGS patients than in either MCD patients or normal control subjects (both P <.01). The urinary GPX level was also significantly lower in FSGS patients than in either MCD patients (P <.05) or normal control subjects (P <.01). The immunostaining score of glomerular GPX was significantly lower in FSGS patients than in normal control subjects (both P <.05). Serial examinations of glomerular GPX immunostaining in FSGS rats also demonstrate a decrease in the score with the progression of disease. Our results indicate that all the plasma, urinary, and glomerular GPX levels are decreased in FSGS patients, indicating a decreased antioxidant defense in the early stages of chronic glomerular diseases. 相似文献
10.
11.
Saleh MA Pollock JS Pollock DM 《The Journal of pharmacology and experimental therapeutics》2011,338(1):263-270
Selective endothelin A (ET(A)) and combined ET(A) and ET(B) receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible for producing the potential benefits have not been discerned. Thus, we determined the actions of ET(A) and ET(B) receptors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats through the use of selective and combined antagonists. Six weeks after streptozotocin (STZ)-induced hyperglycemia, rats were given 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627) (5 mg/kg/day), a selective ET(A) antagonist; (2R,3R,4S)-4-(benzo[d][1,3]dioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-(2-(N-propylpentylsulfonamido)ethyl)pyrrolidine-3-carboxylic acid hydrochloride (A-182086) (10 mg/kg/day), a combined ET(A/B) antagonist; or vehicle for 1 week. Sham controls received STZ vehicle (saline). Hyperglycemia led to significant proteinuria, increased glomerular permeability to albumin (P(alb)), nephrinuria, and an increase in total matrix metalloprotease (MMP) and transforming growth factor-β1 (TGF-β1) activities in glomeruli. Plasma and glomerular soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were elevated after 7 weeks of hyperglycemia. Daily administration of both ABT-627 and A-182086 for 1 week significantly attenuated proteinuria, the increase in P(alb), nephrinuria, and total MMP and TGF-β1 activity. However, glomerular sICAM-1 and MCP-1 expression was attenuated with ABT-627, but not A-182086, treatment. In summary, both selective ET(A) and combined ET(A/B) antagonists reduced proteinuria and glomerular permeability and restored glomerular filtration barrier component integrity, but only ET(A)-selective blockade had anti-inflammatory and antifibrotic effects. We conclude that selective ET(A) antagonists are more likely to be preferred for the treatment of diabetic kidney disease. 相似文献
12.
Renal expression of tissue factor pathway inhibitor and evidence for a role in crescentic glomerulonephritis in rabbits. 总被引:4,自引:0,他引:4
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J H Erlich J Apostolopoulos T C Wun K K Kretzmer S R Holdsworth P G Tipping 《The Journal of clinical investigation》1996,98(2):325-335
Tissue factor pathway inhibitor (TFPI) was demonstrated in the kidneys of normal rabbits and in a crescentic model of glomerulonephritis (GN), where fibrin is a key mediator of injury. In normal kidneys, TFPI was expressed in glomeruli, in intrarenal arteries and the interstitial capillary network. Evidence for TFPI synthesis in vivo was provided by in situ demonstration of TFPI mRNA in glomeruli and intrarenal vessels and by biosynthetic labeling of TFPI released from glomeruli in vitro. In fibrin-dependent crescentic GN, glomerular TFPI synthesis and expression was initially decreased (TFPI antigen at 24 h, 7.5 +/- 0.7 ng/10(3) glomeruli; normal, 11.1 +/- 0.9 ng/10(3) glomeruli, P < 0.02) and subsequently returned to normal values. Plasma TFPI levels increased progressively throughout the evolution of disease. In vivo inhibition of TFPI using an anti-TFPI antibody during the development of GN significantly increased glomerular fibrin deposition (GFD) and exacerbated renal impairment. Infusion of recombinant human TFPI significantly reduced development of GFD (fibrin scores, TFPI treated 0.82 +/- 0.11, control 1.49 +/- 0.14, P < 0.01), proteinuria and renal impairment. This data indicates that TFPI is synthesized and expressed in normal glomeruli and is down regulated in the early response to glomerular injury. Endogenous glomerular TFPI and treatment with recombinant TFPI reduces GFD and injury in fibrin dependent GN. TFPI has the potential to be of therapeutic benefit in the management of fibrin dependent human GN. 相似文献
13.
To evaluate the effect of a rabbit anti-rat macrophage serum (AMS) on glomerular cells in vivo, glomeruli were isolated from an accelerated autologous form of nephrotoxic serum nephritis (NTSN) in rats and grown in tissue culture. The prominent feature of the glomerular outgrowth of the glomeruli in the NTSN was the presence of large numbers of type III (macrophages) cells, which were not present in cultured normal glomeruli. In addition, there were significantly greater numbers of type II (mesangial) cells in culture from the NTSN rats as compared with glomeruli from normal rats though the numbers of type I (epithelial) cells were the same. The administration of AMS prevented the outgrowth of macrophages and reduced the number of mesangial cells in the outgrowth of glomeruli from the NTSN rats. The AMS-treated rats showed profound reduction in proteinuria. Light micrographs showed only minor histologic lesion in the AMS-treated rats. These findings suggest that AMS may be applicable to the modulation of the proliferative response seen in NTSN. 相似文献
14.
Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease 总被引:1,自引:0,他引:1
Kamijo A Kimura K Sugaya T Yamanouchi M Hikawa A Hirano N Hirata Y Goto A Omata M 《The Journal of laboratory and clinical medicine》2004,143(1):23-30
Previous studies have indicated that in massive proteinuria, free fatty acids (FFAs) bound to albumin were overloaded in the proximal tubule and exacerbated tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in the proximal tubule of human kidney. We sought to evaluate urinary L-FABP as a clinical marker in chronic renal disease. Urinary L-FABP was measured in patients with nondiabetic chronic renal disease (n = 120) with the use of a newly established ELISA method. We then monitored these patients for 15 to 51 months. Clinical data were analyzed with multivariate analysis. Urinary L-FABP was correlated with urinary protein, urinary alpha(1)-microglobulin, and serum creatinine concentrations. Urinary L-FABP at the start of follow-up (F = 17.1, r =.36, P <.0001) was selected as a significant clinical factor correlated with the progression rate, defined as a slope of a reciprocal of serum creatinine over time. We next selected the patients with mild renal dysfunction (n = 35) from all 120 patients and divided them into 2 groups according to progression rate: the progression group (n = 22) and the nonprogression group (n = 13). Serum creatinine and urinary protein concentrations and blood pressure at the start of follow-up were higher in the progression group than in the nonprogression group, although we detected no significant difference between the 2 groups. Urinary L-FABP was significantly higher in the former group than in the latter (P <.05). The results showed that urinary L-FABP reflected the clinical prognosis of chronic renal disease. Urinary L-FABP may be a clinical marker that can help predict the progression of chronic glomerular disease. 相似文献
15.
Increased glomerular and extracellular malondialdehyde levels in patients and rats with focal segmental glomerulosclerosis 总被引:1,自引:0,他引:1
Kuo HT Kuo MC Chiu YW Chang JM Guh JY Chen HC 《European journal of clinical investigation》2005,35(4):245-250
BACKGROUND: Evidence suggests an increase in oxidative stress in patients with chronic kidney disease, as glomerulosclerosis is the prerequisite for chronic kidney disease; whether the oxidative stress already exists early on is not known. MATERIALS AND METHODS: In this study we measured the plasma and urinary levels of malondialdehyde (MDA), the end product of lipid peroxidation, and assessed the immunoreactivity of MDA and superoxide dismutase (SOD) in glomeruli of patients and rats with primary focal segmental glomerulosclerosis (FSGS), and compared our findings with those of minimal change disease (MCD) and normal controls (NC). RESULTS: Our results showed that plasma MDA level was significantly increased in patients with FSGS compared with both patients with MCD and normal controls. The urinary MDA level was also significantly increased and was significantly correlated with plasma MDA level in patients with FSGS. The immunostaining for glomerular MDA and SOD was significantly higher in the patients with FSGS than in either the patients with MCD or NC, and was also significantly higher in rats with puromycin aminonucleoside (PAN)-induced FSGS than in rats with MCD. Glomerular MDA level was significantly correlated with the degree of glomerulosclerosis in the patients with FSGS. CONCLUSIONS: Our data suggest that oxidative stress occurs early on before the onset of renal failure, and may play an important role in the pathogenesis of glomerulosclerosis. 相似文献
16.
Role of the terminal complement pathway in experimental membranous nephropathy in the rabbit. 总被引:12,自引:3,他引:12
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G C Groggel S Adler H G Rennke W G Couser D J Salant 《The Journal of clinical investigation》1983,72(6):1948-1957
Our recent observations of a complement-mediated, cell-independent mechanism of altered glomerular permeability in rat membranous nephropathy suggested a possible role for the terminal complement pathway in the mediation of proteinuria in certain forms of glomerular disease. To directly determine whether the membranolytic terminal complement components (C5b-C9) are involved in glomerular injury, we studied the development of proteinuria in normal and C6-deficient (C6D) rabbits, in both of which a membranous nephropathy-like lesion develops early in the course of immunization with cationized bovine serum albumin (cBSA) (pI 8.9-9.2). C6 hemolytic activity of C6D was 0.01% that of control rabbits. After 1 wk of daily intravenous injections of cBSA, proteinuria developed in 71% of controls (median 154, range 1-3,010 mg/24 h, n = 24), whereas none of C6D were proteinuric (median 6, range 2-12 mg/24 h, n = 12, P less than 0.01). After 1 wk of cBSA, both groups had qualitatively identical glomerular deposits of BSA, rabbit IgG, and C3 on immunofluorescence microscopy, predominantly subepithelial electron-dense deposits on electron microscopy, and minimal glomerular inflammatory cell infiltration of glomeruli. Glomeruli were isolated from individual animals after 1 wk of cBSA and deposits of rabbit IgG antibody were quantitated by a standardized in vitro assay using anti-rabbit IgG-125I. Rabbit IgG deposits were found to be similar in control (29.8 +/- 13.2, range 12.7-48.6 micrograms anti-IgG/2,000 glomeruli, n = 6) and C6D rabbits (32.6 +/- 13.8, range 16.8-48.8 micrograms anti-IgG/2,000 glomeruli, n = 5, P greater than 0.05). After 2 wk, coincident with a prominent influx of mononuclear cells and neutrophils, proteinuria developed in C6D rabbits. These results document, for the first time, a requirement for a terminal complement component in the development of immunologic glomerular injury. Since the only known action of C6 is in the assembly of the membrane attack complex, these observations suggest that the membranolytic properties of complement may contribute to glomerular damage. 相似文献
17.
L G Hunsicker T P Shearer S B Plattner D Weisenburger 《The Journal of experimental medicine》1979,150(3):413-425
We have investigated the pathogenesis of glomerular hypercellularity seen in acute serum sickness nephritis induced in rabbits with bovine serum albumin (BSA). The increase in cellularity began with the first stages of immune clearance of BSA, with a peak cellularity occuring at the time of onset of proteinuria. Although there was a significant increase in the fraction of glomerular cells incorporating [3H]thymidine, first seen at the onset of proteinuria, this increase occurred too late and was too small to explain the observed rate of increase in glomerular cellularity. On the other hand, a striking monocytic infiltration of the glomeruli was documented by electron microscopy and by staining for nonspecific esterase. This monocytic infiltration paralleled the observed course of glomerular hypercellularity and was quantitatively sufficient to explain the total increase seen. It appears, therefore, that glomerular hypercellularity seen in this model is principally a result of monocyte infiltration. 相似文献
18.
M A Rahman M Nakazawa S N Emancipator M J Dunn 《The Journal of clinical investigation》1988,81(6):1945-1952
We examined glomerular synthesis of the 5-lipoxygenase metabolite, LTB4, in normal and immune-injured rat glomeruli. Glomeruli isolated from normal rats and from rats with nephrotoxic serum nephritis (NSN), passive Heymann nephritis (PHN) and cationic bovine gamma globulin (CBGG)-induced glomerulonephritis were incubated with the calcium ionophore A23187 (3 microM). Lipids in the glomeruli and media were extracted with ethyl acetate, and were purified and fractionated by HPLC. Immunoreactive-LTB4 (i-LTB4) was determined by radioimmunoassay on HPLC fractions with a detection limit of 50 pg of i-LTB4. A large peak of i-LTB4 that comigrated with authentic LTB4 was found exclusively in glomeruli isolated from the CBGG-injected rats. Addition of the lipoxygenase inhibitor BW755C (50 micrograms/ml) to glomerular incubation resulted in greater than 90% inhibition of i-LTB4. Synthesis of i-LTB4 by glomeruli from normal, NSN and PHN rats was undetectable. Glomerular LTB4 synthesis by CBGG-injected rats was confirmed by radiometric HPLC and by gas chromatography mass-spectroscopy (GC-MS) analysis. In order to rule out synthesis of LTB4 by neutrophils entrapped in the glomeruli, a group of rats received 1,000 rad total body x irradiation, with shielding of the kidneys before induction of CBGG glomerulonephritis. Despite greater than 95% reduction in total leukocyte count, glomerular synthesis of LTB4 remained enhanced. Augmented glomerular synthesis of the proinflammatory lipid, LTB4, in the CBGG model of glomerular disease could have an important role in the development of glomerular injury and proteinuria. 相似文献
19.
Chebotareva NV Bobkova IN Varshavskiĭ VA Golitsyna EP Kozlovskaia LV 《Terapevticheski? arkhiv》2006,78(5):17-21
AIM: To estimate expression of smooth muscle alpha-actin (a-SMA) in renal glomeruli and interstitium of patients with chronic glomerulonephritis (CGN) for assessment of the disease progression and prognosis. MATERIAL AND METHODS: Expression of a-SMA in renal tissue was studied immunohistochemically, area of the interstitium and the degree of its interstitial inflammatory infiltration were investigated morphometrically in 45 biopsy specimens of renal tissue from patients with different morphological types of CGN and 7 specimens of normal renal tissue. RESULTS: a-SMA expression in the glomeruli was higher in patients with proliferative morphological forms of CGN [34.3% (26.1-40.6)] than in patients with nonproliferative nephritis forms [22.3% (18.5-22.3)], p < 0.001; it was the highest in patients with sclerotic alterations in the glomeruli [55.3% (37-61.8)], p < 0.01. The degree of a-SMA expression in renal interstitium of CGN patients correlated most closely with severity of tubulo-interstitial fibrosis (Rs = 0.08, p < 0.001). There was no significant correlation between glomerular a-SMA expression in renal biopsies and proteinuria, creatinine level in the serum of CGN patients, while a-SMA interstitial expression correlated both with severity of proteinuria (rs = 0.5, p < 0.05) and that of renal failure (rs = 0.7, p < 0.001). CONCLUSION: High expression of a-SMA in CGN occurs both in the glomeruli and interstitium of the kidney and evidences for activation of fibrogenesis but only interstitional expression can be considered as a morphological sign of CGN progression and as a factor of an unfavourable prognosis. 相似文献
20.
目的 探讨局灶性节段性肾小球硬化(FSGS)患者血清对体外培养足细胞凋亡和黏附功能的影响.方法 提取原发性FSGS患者和正常人血清,分别以20%正常血清、5%、10%、20%FSGS血清孵育体外培养足细胞24 h.48 h,乳酸脱氢酶(LDH)释放实验检测足细胞活力,Hoechst33258法检测足细胞凋亡率,分光光度法检测足细胞caspase-3酶活性,并检测足细胞黏附能力.结果 FSGS患者血清呈时间和浓度依赖性地升高足细胞LDH释放率(与同时间点正常血清组比较,P分别相似文献