Abstract:
BACKGROUND:Tumor necrosis factor (TNF)-alpha rapidly primes neutrophils (PMN) for an anti-neutrophil cytoplasmic antibody (ANCA)-induced respiratory burst and is thus proinflammatory. TNF-alpha also progressively accelerates apoptosis. We investigated the effect of TNF-alpha-mediated apoptosis on ANCA antigen expression and on ANCA-induced superoxide generation in human PMN. METHODS:PMN were brought to apoptosis by 10 ng/mL of TNF-alpha or a combination of TNF-alpha and 2.5 microg/mL cycloheximide, a protein synthesis inhibitor, or cycloheximide alone for three hours. Apoptosis and ANCA antigen expression were assessed by fluorescence-activated cell sorting (FACS) and microscopy. Superoxide was determined with the ferricytochrome C assay. RESULTS:TNF-alpha with cycloheximide for three hours caused apoptosis in 87% PMN compared to 2% in untreated controls (N=18; P < 0.01). Accelerated apoptosis was associated with an increase in ANCA-antigen expression for both proteinase 3 and myeloperoxidase (P < 0.05). Nevertheless, apoptosis was paralleled by a decreased proteinase 3 and myeloperoxidase ANCA-induced respiratory burst (P < 0.05). Furthermore, superoxide release in response to immune complexes, phorbol ester (PMA), and bacterial peptide (FMLP) was significantly decreased. Blocking caspase-3 activity prevented apoptosis in TNF-alpha with cycloheximide-treated cells (83% to 2%) and prevented compromised respiratory burst in response to ANCA. Caspase-3 inhibition abrogated apoptosis-mediated ANCA antigen up-regulation (PR3 141.6 +/- 34.1 MFI to 33.9 +/- 7.8; MPO 48.3 +/- 12.9 MFI to 11.9 +/- 3.2, N=6, P < 0.05). CONCLUSIONS:TNF-alpha-accelerated apoptosis was associated with increased ANCA antigen expression but with down-regulated respiratory burst activity in response to ANCA. Specific inhibition of apoptosis by caspase-3 blockade prevented the increase in ANCA-antigen expression and preserved the capability of generating superoxide, thereby establishing a causative role for apoptosis. We suggest that TNF-alpha exhibits dual actions by both priming and terminating ANCA-mediated activation of human PMN.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Kettritz R,Scheumann J,Xu Y,Luft FC,Haller Hdoi
10.1046/j.1523-1755.2002.00161.xsubject
Has Abstractpub_date
2002-02-01 00:00:00pages
502-15issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48238-9journal_volume
61pub_type
杂志文章abstract::As an alternative to classical immunosuppressants in experimental lupus nephritis, we looked at bindarit, 2-methyl-2-[[1-phenylmethyl)-1H-indazol-3-y1]methoxy]propanoic acid, a novel molecule devoid of immunosuppressive effects, which selectively reduces chronic inflammation in rat adjuvant arthritis. Two groups of NZ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00804.x
更新日期:1998-03-01 00:00:00
abstract::Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.122
更新日期:1983-07-01 00:00:00
abstract:BACKGROUND:In the United States, infection is second to cardiovascular disease as the leading cause of death in patients with end-stage renal disease (ESRD), and septicemia accounts for more than 75% of this category. This increased susceptibility to infections is partly due to uremia, old age, and comorbid conditions....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00337.x
更新日期:2000-10-01 00:00:00
abstract::IgG4-related disease is a recently recognized multi-organ disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive cells into several organs. Although the pancreas was the first organ recognized to be affected by IgG4-related disorder in the syndrome of autoimmune pancreatitis, we pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.271
更新日期:2010-11-01 00:00:00
abstract::Previous studies in living animals have suggested that variations in the serum concentrations of calcium and phosphate directly affect renal tubular bicarbonate transport. To examine this area more directly, we measured the bicarbonate and the fluid transport in isolated rabbit proximal convoluted and straight tubules...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.43
更新日期:1982-03-01 00:00:00
abstract::Both single-frequency bioimpedance and multiple-frequency spectroscopy are equally accurate in measuring total-body water and intracellular fluid. Estimates are consistent at a population level but not at the individual level, because of wide limits of agreement. There is no real 'gold standard' method providing estim...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.434
更新日期:2014-04-01 00:00:00
abstract::Chronic kidney disease (CKD) is usually associated with interstitial leukocytic cell infiltrates, which may contribute to disease progression by production of proinflammatory, proapoptotic, and profibrotic mediators. Recruiting leukocytes into the kidney involves local expression of chemotactic cytokines, that is, che...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000053
更新日期:2006-01-01 00:00:00
abstract::In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.312
更新日期:1989-12-01 00:00:00
abstract::Erythropoiesis stimulating agent (ESA) treatment has been a major advance in the care of patients with kidney disease, resulting in reduced symptoms and blood transfusions, and improved quality of life. Recent studies, however, have indicated that attempts to treat to near normal Hgb targets may result in increased ri...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.467
更新日期:2009-02-01 00:00:00
abstract::Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contralumi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.12
更新日期:1977-02-01 00:00:00
abstract::Spontaneous and aspirated blood samples were collected from the welling points of surface efferent arterioles in the rat kidney. The amount of tubular reabsorbate in each sample was calculated from measurements of the inulin concentration in the sample and systemic arterial plasma. Both spontaneous and aspirated sampl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.44
更新日期:1984-03-01 00:00:00
abstract::The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.141
更新日期:1981-09-01 00:00:00
abstract::In view of the increasing concern about methicillin-resistant Staphylococcus aureus (MRSA) infections, we studied the characteristics and outcome of MRSA nasal carriage and infections in our CAPD program. All patients entering into the CAPD program from January 1989 to December 1991 were enrolled into the study. The p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.191
更新日期:1993-06-01 00:00:00
abstract::Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl(-) channel activity in Xenopus oocytes. Background. Cyst expansion in autosomal-dominant polycystic kidney disease (ADPKD) is characterized by active Cl(-) secretion in excess of solute reabsorption. However, the connections between elevated epith...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00441.x
更新日期:2005-08-01 00:00:00
abstract::Cilnidipine, a dual L-/N-type calcium channel blocker, dilates both efferent and afferent arterioles and is renoprotective. Our multi-center, open-labeled, and randomized trial compared the antiproteinuric effect of cilnidipine with that of amlodipine in hypertensive patients with kidney disease. A group of 339 patien...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.ki.5002623
更新日期:2007-12-01 00:00:00
abstract::To assess the comparative effects of hemodialysis with acetate versus bicarbonate base on left ventricular systolic function, we performed M-mode echocardiography on 36 patients prior to and immediately following 4-hr maintenance hemodialysis. Patients were initially dialyzed against either sodium acetate or sodium bi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.78
更新日期:1985-05-01 00:00:00
abstract::Since the kidney medulla was reported to generate platelet activating factor (PAF), we investigated a possible effect of this agent on the reabsorptive function of in vitro microperfused medullary thick ascending limbs from mouse kidney (mTAL). PAF, 10(-7) M in the bath, significantly decreased the net chloride flux (...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.38
更新日期:1992-02-01 00:00:00
abstract::In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg bo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.120
更新日期:1990-05-01 00:00:00
abstract::Hypertriglyceridemia in nephrotic (NS) and Nagase analbuminemic rats (Analb) results from reduced triglyceride clearance. NS and Analb have reduced or absent albumin, reduced plasma oncotic pressure (pi), but Analb lack proteinuria. The heparin releasable lipoprotein lipase (LpL) pool in both models is greatly reduced...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000318
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:We developed an electroporation-mediated gene transfer method targeting glomerular mesangial cells. Injecting DNA solution via renal artery followed by electric pulses using tweezers-type electrodes could result in efficient transfection in mesangial cells. Therefore, this gene transfer system opened a feasi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00777.x
更新日期:2004-08-01 00:00:00
abstract::To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.90
更新日期:1993-03-01 00:00:00
abstract::Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000273
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Heparins are currently the anticoagulants of choice in long-term hemodialysis (HD). Because of their shortcomings, including the increasing incidence of heparin-induced thrombocytopenia (HIT II), alternative anticoagulation is necessary. The study objectives were to provide safe and effective HD by investiga...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00433.x
更新日期:2004-02-01 00:00:00
abstract::In Australia, Canada, New Zealand, and the United States indigenous people have high rates of chronic kidney disease but poor access to effective therapies. To more fully define these issues, we compared the demographics of renal transplantation of indigenous patients in these 4 countries. Data encompassing 312,507 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.236
更新日期:2009-09-01 00:00:00
abstract::Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001966
更新日期:2006-12-01 00:00:00
abstract::The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was asse...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.186
更新日期:1995-05-01 00:00:00
abstract::Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-ac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.75
更新日期:1991-04-01 00:00:00
abstract::Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.201
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Regular monitoring of dialysis grafts is recommended, but the value of dialysis graft blood flow monitoring and venous pressures in predicting subsequent outcomes are controversial. METHODS:Over a period of one month, we performed simultaneous flow and venous pressure monitoring in 71 dialysis patients with...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2001.060002762.x
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:We aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene. METHODS:A partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00143.x
更新日期:1998-11-01 00:00:00