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J B Foidart

Publications and source records attributed to J B Foidart.

35 records · Page 2Linked to original sources

Fc-receptor function in Henoch-Schönlein disease of childhood.

The Fc-receptor function of circulating monocytes (CM) and/or of splenic macrophages (SM) was followed in eight children presenting with rheumatoid purpura. The Fc-receptor of CM and/or of SM was decreased in all cases during the acute phase of the disease without any correlation with the plasma values of C3, C4, C3PA or immune complexes. When a clinical improvement occurred, a reversal of the Fc-receptor blockade was noted. In contrast, the Fc-receptor function remained abnormal in three children with persistent nephritis. The sequential measurement of Fc-receptor function may be of predictive value in rheumatoid purpura of childhood.

Antigen-Antibody Complex↗

Fc-receptor function in minimal change nephrotic syndrome of childhood.

This study was undertaken to establish whether the Fc-receptor function of circulating monocytes (CM) and/or of splenic macrophages (SM) is modified during the course of minimal change nephrotic syndrome (MCNS) of childhood. The Fc-receptor function of SM was ascertained by measuring the spleen to liver uptake ratio 40 min after IV injection of heat-damaged autologous erythrocytes labeled with 99Tc, whereas the Fc-receptor function of CM was determined by a "rosetting" test. The Fc-receptor function was followed in six girls presenting with a MCNS and receiving no therapy at the time of testing. The Fc-receptor function of SM was decreased in five patients during an acute phase of MCNS. In four of these five patients, the Fc-receptor function of CM was also altered. No significant correlations were observed between the Fc-receptor blockade and the C3, C3d, C4, C3PA or immune complex-plasma levels. The Fc-receptor blockade was persistent in three girls during remission. A prior incubation of CM with trypsin did not completely reverse the Fc-receptor blockade. Further studies are now being pursued in order to determine whether this persisting abnormality is inherited and mainly observed in relapsing nephrotic syndrome.

Adolescent↗

Accumulation of several basement membrane proteins in glomeruli of patients with preeclampsia and other hypertensive syndromes of pregnancy. Possible role of renal prostaglandins and fibronectin.

The glomerular lesions of preeclampsia consist of swelling of endothelial cells, interposition of mesangial cells and matrix between the endothelial cells and the glomerular basement membrane, and organization of subendothelial deposits of incompletely characterized material. Fibrin and immunoglobulins have previously been localized to these deposits. Laminin, a large basement membrane glycoprotein, type IV collagen, fibronectin, and a basement membrane proteoglycan were found in moderate amounts in the mesangium and prominently in the thickened glomerular capillary walls of patients with preeclampsia or other hypertensive syndromes of pregnancy. Fibrin showed the same pattern of distribution as that of fibronectin. The material deposited in the subendothelial layer of the capillary loops thus consists not only of plasma-derived proteins but also structural components of the glomerular basement membrane and of the mesangial matrix. Type I collagen deposits were demonstrated only in mesangium of pregnant patients with chronic or recurrent hypertension. Glomerular epithelial and mesangial cells synthesize in vitro the basement membrane proteins that accumulate in glomeruli of pregnant hypertensive patients. We have tested the influence of some of the pathophysiologic changes occurring during preeclampsia on the biosynthesis of collagen by rat glomerular epithelial and mesangial cells. Addition of indomethacin to the cultures transiently inhibited the synthesis of prostaglandins (PGE2) and of collagen. Addition of exogenous fibronectin to the media stimulated the production of collagen by mesangial and epithelial cells. Alterations in the metabolism of prostaglandins and the increased deposition of fibronectin observed during preeclampsia could thus play a pathogenic role in the accumulation of basement membrane proteins in glomeruli of these patients.

Basement Membrane↗

Evidence for a particular binding capacity of rat peritoneal macrophages to rat glomerular mesangial cells in vitro.

The adhesion of normal rat peritoneal macrophages to normal rat glomerular epithelial or mesangial cells has been studied in vitro after a 60 min incubation at 37 degree C. After washing, the cell preparations were examined by phase contrast or scanning electron microscopy. Quantitative studies were also performed using macrophages labelled with 99mTc tin colloids. Peritoneal macrophages predominantly adhered to the cultured mesangial cells. The percent-age of labelled macrophages adhering to these cells was about 10 times higher than that of labelled macrophages adhering to the cultured epithelial cells. This percentage increased proportionally to the number of labelled macrophages added, and was strongly reduced by the prior incubation of macrophagic cells with aggregated IgG, with anti-fibronectin IgG, or with F(ab')2 fragments of anti-fibronectin IgG. Furthermore, the macrophage-mesangial cell interaction was significantly reduced by the prior incubation of mesangial cells with anti-fibronectin IgG or with F(ab')2 fragments of anti-fibronectin IgG. The data demonstrate that normal rat peritoneal macrophages preferentially adhere in vitro to normal rat glomerular mesangial cells, and that this binding may be modulated, at least, by: (a) the Fc receptor binding activity of macrophages; (b) the fibronectin molecules available at the surface of macrophages and of mesangial cells.

Animals↗

Effects of a diet deficient in essential fatty acids on the glomerular hypercellularity occurring in the course of nephrotoxic serum nephritis in rats.

An accelerated model of nephrotoxic serum nephritis (NTN) was induced in two groups of Sprague-Dawley rats on the following regimens: (a) a diet deficient in essential fatty acids that contained 20% coconut oil (rats A); (b) a diet supplemented with essential fatty acids that contained 20% safflower oil (rats B). Animals from both groups developed a severe proteinuria reaching its maximum 4 days after the injection of nephrotoxic serum (NTS). Kidney tissue was studied by light and immunofluorescent microscopy 2 to 21 days after NTS injection. The glomeruli of rats A exhibited much more fibrinoid deposition than did those of rats B. A comparable glomerular infiltration by mononuclear cells was observed in both groups of animals between the 2nd and 5th day following the injection of NTS. The number of intrinsic glomerular cells incorporating 3H-thymidine in vivo, however, was significantly lower in rats A than it was in rats B. The outgrowth capacity of glomerular cells in vitro was significantly lower in glomerular explants from rats A than it was in glomerular explants from rats B. These findings demonstrate that, in this model of rat NTN, a diet deficient in essential fatty acids has no major effects on the course of the disease during the first 3 weeks following NTS injection. They further show that the proliferation of intrinsic glomerular cells can be modulated by altering prostaglandin metabolism.

Animals↗

Proliferative glomerulonephritis in rats: evidence that mononuclear phagocytes infiltrating the glomeruli stimulate the proliferation of endothelial and mesangial cells.

A proliferative, non-crescentic, glomerulonephritis (GN) was induced in rats preimmunized with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-GMA IgG. Control rats either received anti-GBM IgG only, or were totally irradiated (800 rads, kidneys protected) 2 days before the second injection. All the GN rats developed a severe proteinuria within 2-4 days after the injection of anti-GBM IgG, contrarily to the control rats. At the same time, many mononuclear cells, of predominantly extra-renal origin, infiltrated the glomeruli. Glomeruli were isolated from GN, normal and control rats and were cultivated in RPMI medium. In normal and control rats cultures, epithelial and mesangial cells were observed. In GN rat cultures, not only epithelial and mesangial cells, but also endothelial and macrophagic cells were identified; the outgrowth capacity of the mesangial cells was enhanced. These data were particularly evident in cultures of GN glomeruli isolated within 2-4 days after the induction of the renal disease, exactly when the glomeruli were infiltrated by a large number of mononuclear phagocytes. It is suggested that the mononuclear phagocytes infiltrating the glomeruli of rats with this model of GN stimulate the proliferation of endothelial and mesangial cells in vitro.

Animals↗

Isolation and characterization of rat renal glomerular cells in vitro.

Glomerular tufts were isolated from normal rat kidneys and were cultivated in RPMI 1640 medium supplemented with 15% fetal bovine serum. Studies on DNA synthesis demonstrated two peaks (A and B) of cell division. The cells of peak A grew as a monolayer until confluency, exhibited many junctional complexes and microvilli. They were very susceptible to the aminonucleoside of puromycin, as glomerular epithelial cells in vivo. They did not contain many bundles of intracellular microfilaments and were not stained by an anti-factor VIII serum. The cells of peak B formed both monolayered sheets and multilayered bands, exhibited no junctional complexes, but contained large bundles of intracellular fibrillar structures, which were strongly stained by an antimyosin antiserum. They were not stained by an anti-factor VIII antiserum. The B cells exhibited a contractile activity in response to 10(-9) M angiotensin II and were very susceptible to mitomycin C treatment, as glomerular mesangial cells in vivo. They synthesized large amounts of prostaglandins (mainly PGE2). The data suggest that the A cells are visceral epithelial cells, and that the B cells are smooth muscle-like cells derived from the glomerular mesangium.

Angiotensin II↗

Synthesis of collagen and fibronectin by glomerular cells in culture.

The biosynthesis of collagen and fibronectin molecules by cultivated glomerular epithelial or mesangial cells was studied at confluency using radioactive proline or lysine as precursors. Collagen represented 0.5% of the total protein synthesized by the glomerular epithelial cells. About 60% of this collagenous protein were associated to the cell layer, whereas about 40% were secreted into the culture medium. Two major collagenous polypeptides were observed with apparent molecular weights of 185K and 170K, and were identified as two gene products of type IV procollagen. They exhibited ratios of 3- to 4-hydroxyproline, of total hydroxyproline to proline, and of hydroxylysine to lysine characteristic of type IV procollagen. They were degraded by bacterial collagenase. The patterns of peptides obtained after digestion of the 185K and 170K chains of this type IV procollagen with pepsin and V8 protease were identical to those obtained after digestion of type IV procollagen chains purified from a murine tumor (EHS sarcoma). Finally. a purified antibody to type IV collagen specifically immunoprecipitated the collagenous protein produced by the glomerular epithelial cells. By contrast, the mesangial cells synthesized about 5% of collagenous protein. 90% of this collagen were secreted into the cultured medium, whereas about 10% remained associated to the cell layer. Type I, III and IV procollagens were synthesized by the mesangial cells. Fibronectin was found in the medium and cell layer of both epithelial and mesangial cells. Fibronectin molecules were identified by their resistance to bacterial collagenase, their susceptibility to pepsin digestion, and their specific adherence to collagen. It was composed of disulfide-linked peptides of 220K daltons. The data therefore demonstrate that: (a) the glomerular epithelial and mesangial cells synthesize fibronectin molecules and type IV procollagen in vitro; (b) the cultivated mesangial cells also synthesize type I and III collagens. The implications of these findings in certain pathological circumstances, such as diabetes mellitus, are now being investigated.

Amino Acids↗

Tissue culture of normal rat glomeruli: glycosaminoglycan biosynthesis by homogeneous epithelial and mesangial cell populations.

The biosynthesis of glycosaminoglycans (GAG) by cultivated rat glomerular epithelial and mesangial cells was studied by incorporation of [35S]sulfate or [14C]glucosamine for 48 h. After dialysis, the incubation medium was subjected to digestion with papain. Labeled GAG were isolated from the digests by precipitation with cetylpyridinium chloride and ethanol. Results of cellulose acetate electrophoresis of the isolated 'epithelial' GAG fraction revealed the presence of two [14C] spots and one [35S] spot. The [35S] spot was identified as heparan sulfate, because it comigrated with the heparan sulfate standard and it was insensitive to testicular hyaluronidase. One [14C] spot comigrated with the [35S] spot and with the heparan sulfate standard. This GAG fraction did not contain galactosamine. The second [14C] spot was identified as hyaluronic acid, since it comigrated with the hyaluronic acid standard and since it was sensitive to testicular hyaluronidase. Results of cellulose acetate electrophoresis of the isolated 'mesangial' GAG fraction revealed the presence of one [14C] spot only. No [35S] spot was detectable. The [14C] spot comigrated with the hyaluronic acid standard and was sensitive to hyaluronidase. The data therefore suggest that the glomerular epithelial cells synthesize and secret both sulfated GAG (heparan sulfate) and nonsulfated GAG (hyaluronic acid) into the culture medium, whereas the glomerular mesangial cells synthesize and secrete nonsulfated GAG (hyaluronic acid) only into the culture medium.

Animals↗

Localization by immunofluorescent microscopy of several collagen types and of a basement membrane proteoglycan in rat glomerular epithelial and mesangial cell cultures.

Confluent cultures of rat glomerular epithelial and mesangial cells were studied by immunofluorescent microscopy, using affinity-purified antibodies directed against collagen of type I-V or an antiserum directed against a basement membrane (BM) proteoglycan. The epithelial cells were stained by antibodies directed against type I, IV and V collagen, whereas the mesangial cells were stained by all the antibodies directed against the different collagenous antigens tested. Therefore, only mesangial cells contained antigenic determinants of type III collagen. On the contrary, both cell types possessed BM proteoglycan antigens. The data suggest that rat glomerular epithelial and mesangial cells may be implicated in the biosynthesis of different components of normal (and pathological) glomerular BM.

Animals↗

Tissue culture of normal rat glomeruli. Isolation and morphological characterization of two homogeneous cell lines.

Glomeruli were isolated from rat kidneys using enzymatic digestion, sieving and differential centrifugation. They were cultured in RPMI medium containing 15 per cent decomplemented fetal bovine serum. Using 3H-thymidine, two peaks of cell division occurred: the first was observed after 2 days in culture and reached its maximum on day 6; the second peak, starting on day 12, reached its maximum on day 22. Two cell types were identified by phase contrast, immunofluorescent and transmission electron microscopy. The first peak contained epithelial cells until day 6, while the second contained smooth muscle-like (mesangial) cells on day 30. The difference in the growth capacity of epithelial and smooth muscle-like cells allows their separate isolation by performing subcultures on day 6 for the former cells and on day 30 for the latter.

Animals↗

Tissue culture of normal rat glomeruli: characterization of collagenous and non-collagenous basement membrane antigens on the epithelial and mesangial cells.

Immunofluorescent studies were performed on epithelial and mesangial cells derived from normal rat glomeruli, using specific antisera directed against insoluble glomerular basement membranes (GMB), or directed against either type IV procollagen or non-collagenous antigens purified from basement membrane polypeptides synthesized by a murine tumour. In marked contrast to the mesangial cells, the epithelial cells contained large amounts of GBM antigens, of type IV procollagen, and of non-collagenous glycoproteins in the first two days after subculture plating. At the same time, the mesangial cells did not exhibit any basement membrane antigens. Five to 10 days later, however, all the antisera tested stained the surface membrane and/or the extracellular material of both epithelial and mesangial cells. The data suggest that both cell lines synthesize and secrete cross-reacting type IV procollagen and non-collagenous basement membrane antigenic material into the culture medium.

Animals↗

Tissue culture of normal rat glomeruli: contractile activity of the cultured mesangial cells.

Rat glomerular epithelial and mesangial cells, and rat skin fibroblasts, were cultured in RPMI medium containing 15% decomplemented fetal bovine serum. They were incubated for 1 h at 37 degrees C with 2 mM [Ca2+]. At that time, their response to various concentrations of angiotensin II, norepinephrine and carbamylcholine was studied by phase contrast microscopy. Only the mesangial cells exhibited contractile activity in the presence of 10(-10) M angiotensin II and 10(-6) M norepinephrine, as demonstrated by the reduction of their length or, more frequently, by modification of their shape. No contractile activity was observed in the presence of 10(-5) M carbamylcholine. The percentage of contractile cells increased proportionally to the concentration of angiotensin II, reaching about 35% with 10(-6) M angiotensin II. The contractile activity was reversible. Specific inhibitors, i.e. Sar1-ala8-angiotensin II and phenoxybenzamine, when administered in concentrations 10 to 100-fold higher than that of the corresponding agonists, completely blocked the contractile response. This competitive effect was also reversible. The data, therefore, suggest that mesangial cells in culture display some functional properties of smooth muscle cells.

1-Sarcosine-8-Isoleucine Angiotensin II↗