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Biomedical subjects

G Andres

Publications and source records attributed to G Andres.

At least 55 records · Page 3Linked to original sources
PubMed1988

Local formation of immune deposits in rabbit renal proximal tubules.

Rabbits passively immunized with goat antibodies to rabbit angiotensin converting enzyme (ACE), an enzyme synthesized in the endoplasmic reticulum and mainly expressed on the apical membranes of the cells of proximal tubules, developed mild and transient immune deposits in this segment of the nephron. Granular deposits of goat IgG, rabbit ACE and C3 were found in the basolateral compartment and were maximal during the first week of immunization when the highest titers of anti-ACE antibodies were present. As the antibody titer fell to an undetectable level, the immune deposits were rapidly cleared and were virtually absent 21 days after the injections. Artificial increase of glomerular permeability allowed focal binding of ACE antibodies to the brush border of some tubules, but did not significantly alter the pattern of immune injury at the base of tubular cells. The data are consistent with the interpretation that the immune deposits result from in situ formation of immune complexes. This mechanism would involve passage of circulating antibodies across the tubular basement membrane and their combination with ACE associated with tubular cell surface membranes.

Animals↗
PubMed1988

Effect of chlorpromazine on the development of experimental glomerulonephritis and Arthus reaction.

Chlorpromazine blocks antibody-mediated redistribution of cell surface antigens in vitro and in vivo and inhibits the development of passive Heymann glomerulonephritis, a disease characterized by in situ formation of immune complexes (Camussi et al J Immunol 1986, 136:2127-2135). The aim of this study was to establish whether chlorpromazine exerts similar effects in other rat models characterized by in situ formation of immune complexes. In glomerulonephritis induced by antibodies reactive with an exogenous antigen "planted" in glomeruli pretreatment with chlorpromazine prevented formation of "humps" and exudative and proliferative lesions. Likewise, chlorpromazine prevented passive reverse Arthus reaction in the skin. In contrast, the drug was ineffective when these lesions were already established, and also failed to inhibit the fulminant course of nephrotoxic serum glomerulonephritis with an enhanced autologous phase. It is proposed that the antiinflammatory effect of chlorpromazine is due to its ability to block the recruitment of inflammatory cells and the release of inflammatory mediators.

Animals↗
PubMed1987

Heymann antibodies induce complement-dependent injury of rat glomerular visceral epithelial cells.

The aim of this study was to investigate the in vitro role of the complement membrane attack complex (MAC) in the injury induced by nephritogenic anti-brush border vesicle (Fx1A) antibodies on rat glomerular visceral epithelial cells (GEC). Both sheep and rabbit anti-rat brush border vesicle IgG-induced complement-dependent lysis of cultured GEC. Fab fragments of sheep anti-rat brush border vesicles and polyclonal or monoclonal gp330 IgG were devoid of lytic activity. Shedding of cell-surface antigens induced by sheep or rabbit anti-rat brush border vesicle IgG protected GEC from subsequent exposure to lytic antibodies and complement, an effect that was not obtained with Fab fragments. When GEC were incubated with sheep or rabbit anti-rat brush border vesicle IgG in capping conditions, the C3 component was co-redistributed with Heymann immune complexes; in contrast, the MAC remained diffusely bound to the cell surface, indicating that it was not associated with the antigen-antibody complexes. The MAC was demonstrated on the surface of GEC by immunofluorescence staining with anti-MAC neoantigen and by electron microscopy of negatively stained membranes showing focal clusters of 110 A MAC lesions. When GEC were treated with sheep IgG or rabbit IgG plus C6-deficient sera, the cells were not lysed and MAC was not demonstrable on the surface; however, lytic activity was restored when C6-deficient sera were reconstituted with purified C6. The results are consistent with the interpretation that injury induced by Heymann antibodies on GEC is MAC-dependent.

Animals↗
PubMed1987

Glomerulonephritis induced in the rabbit by antiendothelial antibodies.

The effects of interaction between endothelial angiotensin converting enzyme (ACE) and goat anti-rabbit ACE (GtARbACE) antibodies were studied in rabbit glomeruli. By immunofluorescence ACE was not detectable in normal glomeruli. However, when kidneys were perfused with GtARbACE antibodies glomerular bound IgG was seven times higher than that of non-immune IgG and granular deposits of goat IgG were found on the endothelium of glomeruli and arteries. Rabbits injected intravenous for 4 d with GtARbACE antibodies showed on day 1 granular deposits of goat IgG on the glomerular endothelium; from day 3 to 24 there was gradual development of subepithelial deposits of goat IgG, rabbit IgG and C3. When GtARbACE antibodies were similarly injected into proteinuric rabbits there was formation of subepithelial granular deposits of goat IgG and ACE. The results document that a glomerular endothelial antigen is redistributed in vivo by a specific ligand, an event associated with formation of immune deposits. Furthermore, if the glomerular permeability is artificially increased, immune complexes shed from nonglomerular endothelia into the circulation can contribute to form subepithelial immune deposits.

Animals↗
PubMed1987

Receptor antagonist of platelet activating factor inhibits inflammatory injury induced by in situ formation of immune complexes in renal glomeruli and in the skin.

Experiments were designed to test the effect of a receptor antagonist of platelet activating factor (PAF), SRI63072, on inflammatory injury induced by in situ formation of immune complexes in two vascular districts of the rat that have different structural and hemodynamic characteristics: unilateral glomerulonephritis induced by perfusion of the left kidney of preimmunized animals with cationic human IgG, and passive reversed Arthus reaction in the skin. Three days after perfusion the left kidneys of rats not treated with SRI63072 (group I) were greatly enlarged, and pale and severe exudative and proliferative lesions were present in glomeruli. Granular deposits of human IgG, rat IgG, and rat C3 were seen by immunofluorescence microscopy, and subepithelial electron-dense deposits were visualized by electron microscopy. The right kidneys were consistently normal. The animals were severely proteinuric and had increased levels of PAF in the circulation. In contrast, rats treated with SRI63072 (group II) and studied at the same interval of time developed only mild, focal glomerulonephritis in the perfused kidneys. By immunofluorescence microscopy the glomerular deposits of human IgG and rat IgG were similar in quantity and distribution to those observed in rats of group I. Despite the fact that SRI63072 did not influence the level or the activity of the rat serum complement system, the deposits of C3 were less abundant and more focal. As in animals of group I, electron-dense deposits were present at the epithelial side of the glomerular basement membrane. Proteinuria was slight, and levels of circulating PAF were not significantly increased. These effects cannot be ascribed to interference of SRI63072 with antigen "implantation," antibody binding, or local hemodynamic conditions, because the amounts of glomerular human and rat IgG were the same in treated and untreated rats; SRI63072 did not decrease the glomerular filtration rate; and SRI63072 prevented the increase in vascular permeability and the exudative lesions in passive Arthus reaction in the skin, a model less affected by hemodynamic changes than glomerulonephritis. The beneficial effect of SRI63072 indicates that PAF is an important mediator of the inflammatory process generated either in glomeruli or in the skin by in situ immune complex formation.

Animals↗
PubMed1987

Lung injury mediated by antibodies to endothelium. II. Study of the effect of repeated antigen-antibody interactions in rabbits tolerant to heterologous antibody.

The effect of repeated interactions of antibodies with cell surface antigens have been examined in in vitro, but not in in vivo systems. In this study are described the results of multiple antibody-cell surface antigen interactions in vivo. Rabbits were given repeated intravenous injections of goat antibodies to angiotensin converting enzyme (ACE), an antigen expressed on the surface of lung endothelial cells. For prevention of anaphylactic reactions, which would have been induced by multiple injections of heterologous immune or nonimmune IgG, the rabbits were made neonatally tolerant to goat IgG. Divalent immune IgG given daily for 21 days induced chronic antigenic modulation (antigen disappearance) with resistance to antibody-mediated inflammatory lesions. The rabbits, however, developed degenerative changes of alveolar endothelial and epithelial cells. Administration of immune IgG every other day for 43 days allowed partial reexpression of ACE and was associated with intravascular, but not interstitial, inflammatory changes. In contrast, repeated administration of monovalent immune Fab did not induce antigenic modulation but caused severe, lethal, interstitial pneumonitis. Thus, in this experimental model the development of acute interstitial inflammatory changes correlates with persistence of antigen and is abrogated by disappearance of antigen induced by divalent antibodies. Further, repeated endothelial antigen antibody interactions fail to induce chronic inflammatory or sclerosing lung lesions.

Animals↗
PubMed1986

Pathogenesis of passive Heymann glomerulonephritis: chlorpromazine inhibits antibody-mediated redistribution of cell surface antigens and prevents development of the disease.

Two hypotheses were tested: first, that in LEW rats the interaction of sheep (or rabbit) anti-brush border antibodies with antigens (Heymann antigens) expressed on the plasma membrane of glomerular visceral epithelial cells is characterized by initial redistribution of immune complexes on the cell surface and by subsequent shedding of immune complexes in the subepithelial part of the capillary wall; and secondly, that this interaction is inhibited by chlorpromazine, a drug that displaces calcium ions from binding sites linking the plasma membrane to the cytoskeleton, and which blocks the redistribution of IgG on the surface of B lymphocytes exposed to anti-IgG antibodies. The studies were performed in vitro on cultured LEW glomerular epithelial cells and in vivo in LEW rats. In cultured glomerular epithelial cells exposed at 37 degrees C to anti-brush border IgG, chlorpromazine prevented, in a dose-dependent manner, the redistribution ("capping") of Heymann antigens and the fixation of complement. The renal glomeruli of chlorpromazine-treated LEW rats examined 6 and 48 hr after transfer of anti-brush border antibodies had punctate and, later, punctate and diffuse deposits of sheep (or rabbit) IgG on glomerular epithelial cells, but not similar deposits of rat C3. Moreover, granular subepithelial deposits of sheep (or rabbit) IgG and rat C3, characteristic of passive Heymann glomerulonephritis, did not develop, although deposits of sheep IgG were detected by immunoelectron microscopy on the microvilli of glomerular epithelial cells. Comparative studies on rats with similar reductions in glomerular filtration rates, produced by high doses of chlorpromazine or with renal artery stenosis, showed that the findings were not the consequence of insufficient delivery of antibody to glomerular epithelial cells. The results are consistent with the interpretation that Heymann glomerulonephritis is induced by mechanisms of redistribution of cell surface antigens comparable to those that govern the interaction of surface antigens (or receptors) with appropriate ligands in B lymphocytes and other classical in vitro systems.

Animals↗
PubMed1986

In vivo interaction of antibodies with cell surface proteins used as antigens.

Antibody interactions with cell membrane glycoproteins in vivo exhibit features of aggregation and capping with resultant shedding similar to those events described in several in vitro isolated cell systems. Requirements for divalent ligand binding and participation of cytoskeletal elements are demonstrated in vivo as well. Persistence of antigen in immune complexes with complement interaction in situ appear to be necessary to induce an inflammatory response in vivo. Abrogation of this response occurs when circumstances permit antigenic modulation with disappearance of the immune complex.

Animals↗
PubMed1986

Reabsorption of horseradish peroxidase by proximal tubules in rats with Heymann nephritis.

The distribution of the histochemical protein tracer, horseradish peroxidase, was studied in proximal tubules of rats with Heymann nephritis. Peroxidase reabsorption was substantially reduced in stage 2 of Heymann nephritis, a period during which the brush border of proximal tubules is severely damaged by specific antibodies. Impairment of the reabsorption function could not be attributed either to proteinuria or disturbances of proximal tubule metabolism and appeared to result from loss of microvilli. Recovery of brush border membrane morphology in stage 4 of Heymann nephritis was not accompanied by recovery of the normal capacity to reabsorb peroxidase. Functional deficits resulting from immunologic injury to proximal tubules in Heymann nephritis may persist despite waning of the anti-brush border antibody response and regeneration of the brush border of proximal tubule cells.

Animals↗
PubMed1986

Distribution of basement membrane antigens in glomeruli of mice with autoimmune glomerulonephritis.

Glomerulonephritis was induced in mice by the repeated injection of human glomeruli or purified glomerular basement membrane. The glomerular basement membranes of nephritic animals were observed to develop subepithelial extensions, "spikes." Although normally Type IV collagen is found throughout the full thickness of basement membranes, the "spikes" reacted with antibodies to laminin but not with antibodies to Type IV collagen. It is proposed that in murine autoimmune glomerulonephritis, the visceral epithelial cells produce an excess of laminin.

Animals↗
PubMed1985

In vivo interaction of antibodies with cell surface antigens. A mechanism responsible for in situ formation of immune deposits in the zona pellucida of rabbit oocytes.

It was the aim of this study to test the hypothesis that the interaction of antibodies with antigens expressed on the plasma membrane of cells surrounded by a basement membrane or a basement membrane-like structure results in in situ formation of immune deposits. Ovary was chosen for the experiments because we found that a well-characterized protein, angiotensin-converting enzyme (ACE), is expressed in a diffuse pattern on the plasma membrane of mature oocytes. To investigate the events following the in vivo interaction of oolemma-ACE with its antibody, rabbits were injected with goat anti-rabbit ACE gamma-globulin or with Fab fragments of goat anti-rabbit ACE IgG in an ear vein for a maximum of 4 d; they were followed for up to 20 d thereafter. Ovary tissue was studied by immunofluorescence, and immunoelectron, light, and transmission electron microscopy. The results of this study document two new findings: First, that ACE is expressed on the oolemma of rabbit oocytes. Second, that the in vivo interaction of divalent antibodies to this cell surface antigen induces formation of granular immune deposits in the adjacent zona pellucida through a mechanism of "patching" and "shedding" of immune complexes, similar to that occurring in in vitro systems characterized by interaction of plasma membrane receptors with soluble ligands. This mechanism might have importance in the pathogenesis of Heymann glomerulonephritis and of other immunological diseases involving antigens expressed on the plasma membrane of cells.

Animals↗
PubMed1985

Proximal tubule function in chronic serum sickness glomerulonephritis of rats.

Fatal immune complex glomerulonephritis can be induced in rats by chronic intravenous administration of bovine serum albumin. There are three distinct stages, mild, moderate, and severe, in the development of renal immunopathology and pathophysiology in this model of chronic serum sickness. The work described here was undertaken to evaluate aspects of proximal tubule function in those different stages. Tissue water distribution, oxidative metabolism, and transport of representative organic anions and cations were measured in renal cortical slices. In mild chronic serum sickness all functions were normal except the transport of p-aminohippurate (PAH, organic anion), which was significantly decreased. This decrease appeared to be attributable to immunization with Freund's adjuvant. In the moderate stage of chronic serum sickness, proximal tubule functions and morphology appeared essentially normal. Only Na-K-ATPase activity was somewhat lower than in controls. However, proximal tubule dysfunction was a feature of severe chronic serum sickness. A significant inhibition of anion and cation transport was observed. Reduction in transport functions occurred together with impaired oxidative metabolism and severe reduction in Na-K-ATPase activity. Abnormalities of mitochondrial structure, a decrease in number of mitochondria, and a significant increase in intracellular H2O content provided additional evidence of degenerative changes in proximal tubule cells during the severe stage of chronic serum sickness. It was concluded that decreased transport of organic ions by the basolateral membrane in proximal tubules of rats with severe chronic serum sickness resulted from a breakdown in the metabolic machinery of the tubule epithelium rather than a specific injury to organic ion transport systems.

Animals↗
PubMed1985

Impaired organic ion transport in proximal tubules of rats with Heymann nephritis.

Organic ion transport across the basolateral membrane of proximal tubules was measured by means of the tissue slice technique in each of the four different stages of Heymann nephritis. Impairment of both organic anion and cation transport was detected early in Stage 2, and became more severe in Stage 3 of Heymann nephritis. The decreased transport function was associated with extensive damage to proximal tubule cells, including loss of brush border microvilli and basal infoldings. Despite these abnormalities of structure and function, oxygen consumption of proximal tubule cells remained essentially normal. Partial recovery of organic cation transport was noted late in Heymann nephritis (Stage 4). Recovery of the cation transport function was associated with a partial restoration of brush border microvilli and basal infoldings to proximal tubule cells. However, organic anion transport remained depressed throughout the entire course of disease. Impairment of organic ion transport in rats with Heymann nephritis appeared to result from damage to basolateral membrane transport elements rather than general deterioration of the metabolic machinery of proximal tubule cells. Decreased organic cation transport appeared to be the consequence of a reduction in the number of carrier sites, a phenomenon that could have resulted from decreased membrane surface area. However, the depression of organic anion transport was associated with decreased substrate affinity of the anion carrier, indicating that qualitative, rather than quantitative changes, were primarily responsible for that defect. Specific antibody-mediated damage to the anion transport elements in basolateral membranes of proximal tubules is postulated to occur in Heymann nephritis.

Adjuvants, Immunologic↗