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Biomedical subjects

G Andres

Publications and source records attributed to G Andres.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis.

In patients with glomerulonephritis widespread crescents are associated with a poor prognosis. Crescent formation appears to depend on the migration of mononuclear cells into Bowman's space, and therefore the interaction between leukocytes and glomerular endothelium may be a critical event in the genesis of crescents. We performed the present study to determine the effects of mouse monoclonal antibodies to the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) in a model of crescentic glomerulonephritis in Wistar-Kyoto rats, induced by immunization with bovine glomerular basement membrane (GBM). By 10-14 d after immunization, the rats had developed circulating anti-GBM antibodies, reactive with the alpha 3 chain of type IV collagen (the Goodpasture antigen), accompanied by proteinuria, accumulation of rat immunoglobulin (Ig)G in the GBM, increased expression of ICAM-1 by glomerular endothelial cells, infiltration of glomerular tufts with LFA-1+ T cells and monocyte/macrophages, and early crescents. At 5 wk all rats had diffuse fibrocellular crescents, glomerular sclerosis, and tubulointerstitial damage. All rats developed severe renal insufficiency and died by 5 or 6 wk. The administration of monoclonal antibodies to rat ICAM-1 and LFA-1 markedly decreased the severity of the renal disease. In a group of rats injected three times a week with the monoclonal antibodies, from 2 d before immunization with GBM to day 14, glomerular abnormalities and proteinuria were virtually absent at day 14; even at 5 wk glomerular disease was quite mild, with only slight crescent formation and with only a mild decrease in renal function. When treatment was continued until 5 wk, the beneficial effects were even more marked, with virtual absence of crescents and with preservation of normal renal function. In a group of rats in which treatment was initiated on day 14, shortly after the appearance of glomerular abnormalities, progression of the disease was appreciably retarded, and the decrease in renal function was inhibited. The kidneys of rats treated from days -2 to 14 with antibodies to ICAM-1 and LFA-1 showed bright linear staining for rat IgG along the GBM, which did not differ in intensity from that seen in untreated rats. Furthermore, the titers of anti-GBM antibodies at 2 wk in treated rats were not lower than that seen in most of the untreated rats. There was, however, moderate reduction of anti-GBM antibodies at 5 wk in the treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Role of the membrane attack complex of complement in lung injury mediated by antibodies to endothelium.

The potential pathogenic role of the membrane attack complex (MAC) of the complement system was investigated in two models of lung injury mediated by antibodies to angiotensin-converting enzyme (ACE), an endothelial cell enzyme. In the first model, acute and fatal lung edema was induced in rabbits by intravenous administration of divalent anti-ACE antibodies. These animals died acutely. C6-deficient rabbits tolerated anti-ACE antibodies without apparent ill effects. On the other hand, C6-deficient rabbits reconstituted with C6 and then receiving anti-ACE antibodies developed acute pulmonary edema and died. These results indicate that the MAC is required for the pathogenesis of this lung injury. In the second model, intravenous administration of monovalent anti-ACE Fab fragments over 4 consecutive days induced fatal interstitial pneumonitis in normal rabbits. For C6-deficient rabbits there was a reduced inflammatory response, and no animals died, implicating a mediator function for the MAC in this model as well. These results demonstrate that MAC is an important mediator of acute pulmonary edema induced by divalent antibodies to an endothelial antigen. Moreover, the complement system was also, to some extent, involved in the recruitment of inflammatory cells leading to the development of interstitial pneumonitis in the experimental lung injury induced by monovalent anti-ACE Fab fragments that 'per se' do not activate complement.

Acute Disease↗
PubMed1993

Hyaluronate is a component of crescents in rat autoimmune glomerulonephritis.

BACKGROUND: Crescent formation is a major feature of rapidly progressive glomerulonephritis and is generally associated with a poor prognosis. Crescents are formed by accumulation of monocyte/macrophages and plasma proteins in Bowman's space, by proliferation of parietal epithelial cells and fibroblasts, and by deposition of the extracellular matrix. Interactions of components of the extracellular matrix with surface receptors of inflammatory cells may be important in crescent formation. One such receptor is the glycoprotein, CD44, whose main ligand is hyaluronate. We performed the present study to determine if hyaluronate is a component of crescents in a model of autoimmune anti-glomerular basement membrane nephritis in rats. EXPERIMENTAL DESIGN: Wistar-Kyoto rats were immunized with bovine glomerular basement membrane, that resulted in severe crescentic glomerulonephritis. Sections of renal tissue were studied with two probes to detect hyaluronate: (a) a soluble CD44-human immunoglobulin fusion protein; and (b) a hyaluronic acid-binding protein. Both probes were revealed by immunofluorescence techniques. The specificity of the reactions was established by selective enzymatic digestions. RESULTS: Marked accumulation of hyaluronate was demonstrated in developing and sclerosing crescents, in association with local infiltration of T lymphocytes and monocyte/macrophages, cells known to express CD44. Lesser amounts of hyaluronate were found in periglomerular infiltrates. CONCLUSIONS: Hyaluronate is an abundant extracellular component of crescents, and may play a critical role in their formation, by its effects on migration and activation of CD44+ lymphocytes, monocyte/macrophages, fibroblasts and epithelial cells.

Animals↗
PubMed1993

Detection of two forms of GP330. Their role in Heymann nephritis.

Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain.

Amino Acid Sequence↗
PubMed1992

Antibodies in rabbits immunized with cationized IgG react with histones H3 and H4.

OBJECTIVE: Rabbits immunized with cationized rabbit IgG develop antinuclear antibodies. This study was aimed at identifying the reactive antigens. METHODS: Rabbits were immunized with homotypic or allotypic IgG that were physicochemically altered to produce positively charged dimethylpropanamide (polycationic) side chains. RESULTS: Seven of 11 rabbits injected with cationized IgG produced antinuclear antibodies detected by indirect immunofluorescence. By enzyme-linked immunosorbent assay, these were IgG antibodies reacting with histone (H3-H4)2 tetramer and with individual histone polypeptides H3 and H4. The antihistone antibodies were absorbed by cationized IgG but not by normal IgG. CONCLUSION: Cationized IgG appears to possess antigenic determinants of sufficient similarity to produce antibody responses cross-reactive with histones H3 and H4.

Animals↗
PubMed1992

Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.

Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions.

Animals↗
PubMed1992

[Pathogenesis and therapy of glomerulonephritis. Reflections on recent advances].

The aim of this review is to describe how antibodies and cells of the immune system induce inflammatory lesions in the kidney. Renal glomeruli and tubules can be damaged not only by antibodies and immune complexes generated in the immune system but also by T lymphocyte-mediated hypersensitivity reactions originated locally. New mediators of inflammation have been identified, including growth factors and cytokines which are essential symbols of a language of intercellular communication modulating cell proliferation, the adhesion of inflammatory cells to the walls of the vessels, and to the extracellular matrix, and the formation of fibrosclerotic tissue contributing to the healing process. The identification of new methods for induction of tolerance to histocompatibility antigens, the identification of antigens responsible for autoimmune diseases of the kidney, and the synthesis of the peptides forming the receptor of T lymphocytes involved in the pathogenesis of an autoimmune disease of the brain, may help to design new therapeutic strategies for renal diseases, based on the inhibition of T lymphocyte activation.

Cytokines↗
PubMed1990

Effect of leukocyte stimulation on rabbit immune complex glomerulonephritis.

Phytohemagglutinin (PHA), a leukocyte mitogen, induces a lymphocyte and blast cell glomerulonephritis in rat renal allografts (Cell Immunol 13:146, 1974). The aim of this study was to assess whether PHA similarly enhances rabbit monocyte-dependent experimental, acute immune complex glomerulonephritis, and whether this effect is associated with local release of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Rabbits with experimental acute serum sickness (AcSS: Group I) had focal proliferative and exudative glomerulonephritis with immune deposits, scattered subepithelial electron-dense deposits (humps), mild and transient proteinuria, normal creatinine clearance and slightly increased production of IL-1 and TNF from isolated glomeruli. Rabbits with AcSS and injected with PHA (Group II) developed severe lymphocyte and blast cell glomerulonephritis with diffuse endothelial damage; immune deposits were significantly reduced, focal subepithelial electron-dense deposits were absent, proteinuria was increased, creatinine clearance was decreased and production of IL-1 and TNF was markedly augmented as compared to rabbits in Group I. Rabbits with AcSS and injected with IL-1 beta and TNF alpha (Group V) had lesions comparable to those seen in Group II. These results show that PHA, IL-1 and TNF enhance the severity of acute immune complex glomerulonephritis, presumably by activating glomerular endothelial and mesangial cells and resident or infiltrated leukocytes.

Animals↗
PubMed1990

Pathogenesis of an experimental model of Goodpasture's hemorrhagic pneumonitis.

The mechanisms that allow circulating basement membrane antibodies (Ab) to interact with the alveolar basement membrane (ABM) inducing Goodpasture's hemorrhagic pneumonitis are unknown. In laboratory animals the ABM is inaccessible to phlogogenic amounts of ABM Ab unless the permeability of the unfenestrated alveolar endothelium is increased. This study was designed to test the hypothesis that in the mouse polypeptide mediators, generated by activated lymphoid cells or cells infected by viruses, contribute to the pathogenesis of passive Goodpasture's hemorrhagic pneumonitis. In naive mice that received rabbit ABM Ab, these bound to the glomerular basement membrane but not to the ABM and their lungs were normal. In the lungs of mice injected with human recombinant IL-2 and IFN-alpha specific binding of ABM IgG, C3, and fibrinogen to the ABM, diffuse and severe erythrocyte extravasation, and accumulation of mononuclear and polymorphonuclear leukocytes were constantly observed. ABM Ab and IL-2 or ABM Ab and IFN-alpha did not produce comparable effects. Mice injected only with IL-2 and IFN-alpha had enlarged, edematous lungs without pulmonary hemorrhages. The results show that the synergism of IL-2 and IFN-alpha convert the lung into a preferential target for AMB Ab, suggesting that cytokines may have a role in the pathogenesis of human Goodpasture's pneumonitis.

Animals↗
PubMed1990

Involvement of cytokines and platelet-activating factor in renal pathology.

Platelet-activating factor (PAF) is a phospholipid that exhibits a wide range of biological activities as a secondary mediator of inflammation and anaphylaxis. Primary mediators of inflammation, such as interleukin-1 and tumor necrosis factor, stimulate PAF release by monocytes/macrophages, neutrophils and endothelial cells. PAF has also been implicated in cell-mediated hypersensitivity reactions. This review will focus on recent data suggesting that the local production of these mediators in glomeruli by infiltrating inflammatory cells or resident cells may influence the clinicopathological expression of glomerular disease. Results from in vitro and experimental studies suggest that these mediators alter the growth pattern of glomerular cells and the composition of secreted matrix, leading to scar formation and eventually to glomerulosclerosis.

Acute Kidney Injury↗
PubMed1989

Lung injury in rabbits induced by intravenous administration of heterologous polyclonal antibodies to angiotensin converting enzyme (kininase II).

Antibody interactions with the endothelial cell membrane glycoprotein angiotensin converting enzyme (Kininase II) 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, deposition of complement and participation of cytoskeletal elements are demonstrated in vivo. Persistence of antigen in immune complexes with complement interaction appear to be necessary to induce an inflammatory response. Abrogation of this response occurs when circumstances permit antigenic modulation with removal of the immune complex from the endothelial surface.

Animals↗
PubMed1989

Expression and modulation of surface antigens in cultured rat glomerular visceral epithelial cells.

This study, using immunocytochemical light and electron microscopy techniques, characterizes the distribution of three antibodies bound to the surface of rat glomerular visceral epithelial cells (GEC) in culture, and tests their ability to redistribute corresponding antigens under conditions appropriate for antigenic modulation (antigen disappearance). At 4 degrees C or after fixation, anti-renal tubular brush border vesicle (BBV) IgG bound diffusely to the surface of GEC and to coated pits. Anti-gp330 IgG had a discrete distribution on the surface of GEC and reacted with coated pits. Anti-podocalyxin IgG was bound diffusely to the surface of GEC but not to coated pits. At 37 degrees C, anti-BBV IgG induced marked redistribution of immune complexes with both shedding and internalization. Anti-gp330 IgG induced weaker redistribution, with internalization of immune complexes predominating. Anti-podocalyxin IgG induced rapid redistribution of immune complexes and antigenic modulation but minimal internalization. Experiments of differential redistribution indicated that anti-BBV IgG modulated the expression of both gp330 and podocalyxin; anti-gp330 IgG had a weaker effect on BBV antigens and podocalyxin; and anti-podocalyxin failed to redistribute BBV antigens or gp330. The relevance of these immunocytochemical studies of antibody-cell surface antigen interaction in cultured GEC to understanding the pathogenesis of Heymann glomerulonephritis (HG) is discussed.

Animals↗