Autoimmune Glomerulonephritis Induced in Sheep by Injection of Human Lung and Freund's Adjuvant

Steblay, Raymond William; Rudofsky, Ulrich H.

doi:10.1126/science.160.3824.204

Cited by 47 publications

(8 citation statements)

References 10 publications

(2 reference statements)

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“…Such limited, common antigenic specificity shared by Anti-GBAI Antibodieslung and renal basement membranes has been the subject of several investigations in animal models and is well documented (22)(23)(24), but definition of the restricted specificity of human anti-GBM antibodies, comparing GP and non-GP eluates on homologous substrates has not been done previously. (25).…”

Section: Discussionmentioning

confidence: 99%

Characterization of human anti-glomerular basement membrane antibodies eluted from glomerulonephritic kidneys

McPhaul¹,

Dixon²

1970

J. Clin. Invest.

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A B S T R A C T Eluates from glomerulonephritic kidneys of nine patients with anti-glomerular basement membrane (anti-GBM)-mediated nephritis were studied to define their antigenic specificity and content of kidney-fixing antibodies. Five of these patients had Goodpasture's syndrome with pulmonary and renal involvement clinically; four patients did not. All had in vivo fixation of JgG in the characteristic linear pattern by direct immunofluorescence, and eluted JgG fixed to normal human kidney sections. Eluates from kidneys of patients with Goodpasture's syndrome fixed more frequently to homologous nonglomerular renal and extrarenal antigenic sites and to heterologous GBM than did non-Goodpasture eluates over a hundredfold range of antibody concentrations; both could be blocked by prior absorption with soluble GBM antigens. By radial immunodiffusion and precipitation tests the content of JgG in the eluates was measured to range from 2 to 20% of the total protein eluted. By paired label isotopic fixation studies with some of the eluates the per cent of IgG that was kidney fixing ranged from 0.6 to 23.4%. Although the in vivo fixation studies with radiolabeled eluates failed to indicate significant fixation to monkey lung, the observations define quantitative as well as qualitative differences between anti-GBM antibody populations mediating the Goodpasture syndrome compared to those causing glomerulonephritis without lung involvement. This is publication No. 355 from the

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Section: Discussionmentioning

confidence: 99%

Characterization of human anti-glomerular basement membrane antibodies eluted from glomerulonephritic kidneys

McPhaul¹,

Dixon²

1970

J. Clin. Invest.

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“…Lehman et al [2] also described an anti-TBM-associated nephritis in Brown-Norway (BN) and Lewis (Le) rats immunized with bovine TBM. The histology was the same as that described by Steblay and Rudofsky [1], Furthermore, the mechanisms in volved in the systems seemed to be immunologically similar to several recently de scribed cases of human interstitial dis eases.…”

Section: Introductionmentioning

confidence: 53%

“…After Steblay and Rudofsky [1] described a type of experimental renal tubular disease, it has gradually been clarified that a renal tubular basement membrane antigen plays an important role in the immunopathologic mechanism responsible for interstitialnephritis. Subsequently, the role of anti-TBM antibody in tubular injury has been dis cussed by several authors [2,[15][16][17], Hyman et al [18] described a disease which occurred in inbred systems of guinea pigs and sug gested that anti-TBM antibody formation and the tubular injury as a response might be genetically controlled.…”

Section: Discussionmentioning

confidence: 99%

“…In 1971, Steblay and Rudofsky [1] de scribed a new renal cortical tubular disease in guinea pigs after immunization with rab bits' renal cortical tubular basement mem brane (TBM) with complete Freund's adju vant. The histological manifestations of renal diseases were characterized by focal, cortical, interstitial mononuclear cell infil trates, tubular atrophy, and peritubular fi brosis.…”

Section: Introductionmentioning

confidence: 99%

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Murine Autoimmune Interstitial Nephritis and Associated Antigen: Purification of a Soluble Tubular Basement Membrane Antigen from Mice Kidneys

Wakashin¹,

Wakashin²,

Ueda³

et al. 1980

Kidney Blood Press Res

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A soluble tubular basement membrane (TBM) antigen has been purified from murine kidneys. The isolated fibers were trypsinized and subjected to zone electrophoresis, Sephadex G-200 gel filtration, and DEAE-cellulose chromatography eluted with linear NaCl concentration gradient while monitoring the TBM antigen activity with specific antihuman TBM antigen. The molecular weight of TBM antigen was estimated to be 30,000 daltons by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified TBM antigen gave a single precipitin line against the specific antiserum and cross-reacted with the TBM antigen similarly purified from other animals such as goat, guinea pig and also with human TBM antigen in an immunodiffusion plate. BALB/c, C3H/He and C57BL/6 mice were immunized twice at 2 weeks’ interval with the TBM antigen and adjuvant. Histologically typical interstitial nephritis occurred in BALB/c mice, whereas no nephritis developed in other strains of mice. The inflammatory changes were characterized by intense mononuclear cell infiltration, tubular destruction, and interstitial and periglomerular fibrosis. The serum-stained basement membrane of normal tubules and Bowman’s capsules, and no antiglomerular basement membrane activity was detectable in the serum by immunofluorescence. This system provides a simple and useful model of interstitial nephritis in mice produced with a purified TBM antigen.

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“…It has long been known that injections of antisera to homogenates of lung [1] or placenta [2] could induce glomerulonephri tis in an animal of the species whose tissue was used as an immunogen and that the induced glomerulonephritis was indistin guishable from the disease caused by the injection of antikidney serum. In 1968, Steblay andRudofsky [3] induced autoimmune glomerulonephritis in sheep by injections of human lung and Freund's adjuvant. The nephritis appeared identical to the nephritis induced in sheep by human glomerular basement membrane (hGBM) and resem bled the nephritis in Goodpasture's disease, in which the presence ofcirculating antibod ies to both GBM and alveolar basement membrane (ABM) can often be demon strated.…”

Section: Introductionmentioning

confidence: 99%

Human Basement Membrane Antigens from Lung, Placenta and Kidney

Bray¹,

Turino²,

Mandl³

1980

Kidney Blood Press Res

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Three human basement membranes, glomerular basement membrane (GBM) from renal cortex, alveolar basement membrane (ABM) from lung parenchyma and trophoblast basement membrane (TBM) from the terminal villi of placenta have been isolated by sieving and sonication techniques. Canine GBM and ABM were also prepared. There were marked differences among the membranes from human tissues. Compared to GBM, TBM had very little collagen but contained high concentrations of charged amino acids. ABM was intermediate in composition between GBM and TBM and contained desmosine and isodesmosine indicative of the presence of elastin. Canine ABM (c-ABM) did not contain desmosine or isodesmosine. In the canine system an antigen was detected in ABM which was not present in GBM. The membrane preparations were analyzed for fibronectin content using a specific antiserum to fibronectin. This glycoprotein could not be detected in GBM whereas it was present in ABM in amounts up to 0.8% and in TBM in amounts as high as 7.2%. All the membranes induced the formation of precipitating antibodies in rabbits. Soluble material obtained from the membranes by alkali extraction, reduction of disulfide bonds, enzymatic digestion with elastase, plasmin or collagenase provided immunologically reactive fragments. These soluble fragments gave reactions of identity among the three basement membranes in immunodiffusion reactions in gels with antisera raised to all three BMs. The finding that plasmin digests basement membranes suggests that it may play a role in connective tissue remodeling. The fact that elastase degrades basement membranes provides an endogenous system for injury which may be triggered by infections.

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Autoimmune Glomerulonephritis Induced in Sheep by Injection of Human Lung and Freund's Adjuvant

Cited by 47 publications

References 10 publications

Characterization of human anti-glomerular basement membrane antibodies eluted from glomerulonephritic kidneys

Characterization of human anti-glomerular basement membrane antibodies eluted from glomerulonephritic kidneys

Murine Autoimmune Interstitial Nephritis and Associated Antigen: Purification of a Soluble Tubular Basement Membrane Antigen from Mice Kidneys

Human Basement Membrane Antigens from Lung, Placenta and Kidney

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