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At least 19 recordsLinked to original sources
PubMed1992

Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury.

Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset less than 1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (approximately 54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (approximately 41%), and CD11c (approximately 23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded approximately 27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

An ultrastructural study of proliferative nephritis induced experimentally by a monoclonal antibody against mesangial cells: replacement of mesangial cells by cells of the monocyte-macrophage system.

An experimental nephritis accompanied by transient proteinuria can be produced by an intravenous injection of the monoclonal antibody, 1-22-3, raised against isolated rat glomeruli. The present study deals with the ultrastructural changes in the glomeruli in rats after the injection of this antibody. At 2 h after injection, all the mesangial cells had completely degenerated and neutrophils invaded most mesangial areas. Monocytes occupied the vacant mesangial areas at 24 h and gradually increased in number over the next 4 days. At 4 and 6 days, macrophage-like cells, possibly derived from monocytes, underwent frequent mitosis, resulting in a remarkable proliferation of these cells. The interpretation of these cells as macrophages was strongly supported by the fact that they contained previously injected latex particles in large numbers. From 2 to 4 weeks after injection, the macrophage-like cells gradually transformed into cells indistinguishable from normal mesangial cells. In the present experimental nephritis where all mesangial cells were initially destroyed, cells of the monocyte-macrophage system appear to play a leading role in the pathogenesis of the ensuing proliferative glomerulonephritis, and represent the source of the replacing mesangial cells.

Animals↗
PubMed1992

Cell surface receptors and ectoenzymes in mesangial cells.

Mesangial cells possess a variety of receptors for hormones and autacoids. They are also equipped with ectoenzymes whose function may be to control the availability of autacoids and hormones at their receptor sites. Several examples are considered. Receptors for angiotensin II (AII) are present both on murine and human mesangial cells. One single group of receptors has been demonstrated in each of these preparations. Mesangial cell AII receptors are linked to phospholipase C via a G protein. They belong to the AT1 subtype because (125I)AII is displaced from its binding sites preferentially by AT1 antagonists such as DUP 753 and EXP 3,174, whereas AT2 antagonists are much less potent. AT1 antagonists suppress the biological effects of AII in mesangial cells, including the stimulation of intracellular calcium concentration and the increase of prostaglandin synthesis and of (3H)leucine incorporation. Mesangial cells also have receptors for atrial natriuretic factor, but the distribution between B receptors with guanylate cyclase activity and clearance (C) receptors varies with the species. Both types are present in murine mesangial cells, whereas only C receptors are found in human mesangial cells. In contrast, human epithelial cells possess both B and C receptors. Ecto-5'-nucleotidase activity results in the production of adenosine, which acts on mesangial cells through A1 and A2 receptors. This enzyme is markedly induced in rat mesangial cells by interleukin-1, whose effect is mediated in part by prostaglandin E2 and cAMP. Various other cAMP-stimulating agents also induce 5'-nucleotidase expression in rat mesangial cells. Ectopeptidases are present in all glomerular cell types but essentially in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1992

Sustained activation of PGE2 synthesis in mesangial cells cocultured with glomerular endothelial cells.

Glomerular endothelial cells synthesize and release endothelin-1 (ET-1), and mesangial cells, normally closely apposed to endothelial cells in vivo, respond to ET-1 with contraction, proliferation, and prostaglandin E2 (PGE2) release. This study sought to determine whether chronic coculture of mesangial cells with glomerular endothelial cells alters mesangial cell PGE2 synthesis. Mesangial cells cocultured with endothelial cells were found to release PGE2 at rates much greater than those observed in mesangial cells not cocultured with endothelial cells. This effect persisted for at least 24 h after the mesangial cells were removed from coculture with endothelial cells. The increase in basal mesangial cell PGE2 synthesis was dependent on endothelial cell-derived ET-1. Despite the increase in basal PGE2 synthesis after coculture with endothelial cells, acute ET-1-stimulated PGE2 release was markedly blunted in mesangial cells that had been cocultured with endothelial cells when compared with mesangial cells in solo-culture. This lack of responsiveness was specific for ET-1 and resulted from a profound downregulation of mesangial cell endothelin receptors. Thus coculture with endothelial cells produces two apparently opposing and ET-1-dependent effects in mesangial cells, namely a sustained increase in basal PGE2 synthesis by the cells and a loss of responsiveness to further stimulation with ET-1. It is postulated that the induction of sustained PGE2 synthesis may also occur in vivo if endothelin release from endothelial cells is stimulated and may explain, in part, the extraordinary sensitivity of some patients with glomerular disease to cyclooxygenase inhibitors.

Animals↗
PubMed1992

Effect of amlodipine on mesangial cell proliferation and protein synthesis.

Mesangial cells in the glomerulus have several important physiological functions, as has been demonstrated by past research. Platelet derived growth factor, thrombin, endothelin, and angiotensin II have all been shown to affect mesangial cell growth and protein synthesis. First generation Ca channel blockers also have a definite effect on mesangial cell proliferation. We investigated whether the effects of a second generation Ca channel blocker, amlodipine, were similar. Amlodipine was found to inhibit hyperplasia and hypertrophy in mesangial cells.

Amlodipine↗
PubMed1992

Mesangial cell killing by leukocytes: role of leukocyte oxidants and proteolytic enzymes.

Mesangial cells from human and rat kidney were examined for sensitivity to killing by neutrophils. Cells from both species were sensitive to killing by phorbol myristate acetate-stimulated neutrophils. Catalase was highly protective while superoxide dismutase was less protective and a number of protease inhibitors were not protective. Strong protection was also observed with the iron chelators, deferoxamine and phenanthroline, and with the hydroxyl radical scavengers, dimethylthiourea and 5,5-dimethyl-1-pyrroline N-oxide. Pretreatment of the mesangial cells with deferoxamine followed by washing also provided protection. Mesangial cells were also killed by reagent hydrogen peroxide (H2O2) but were much less sensitive to injury by direct application of proteolytic enzymes. The ability of H2O2 to injure mesangial cells was prevented by pre-incubation of the H2O2 with human leukocyte myeloperoxidase. These data suggest that killing is due primarily to the generation of H2O2 by the stimulated neutrophils and its further reduction in an iron-catalyzed reaction. The hydroxyl radical may be the reduction product that actually mediates lethal injury but lack of scavenger specificity prevents definitively concluding this. Mesangial cell killing by activated neutrophils could be significantly inhibited by monoclonal antibodies to CD11/CD18 molecules, suggesting that close contact between the target and effector cells is required for cytotoxicity. Although qualitatively similar to endothelial cells, the mesangial cells appeared to be quantitatively more oxidant sensitive than previously examined human and rat endothelial cells. Taken together, these data show that mesangial cells from rat and human are sensitive to leukocyte-induced injury and that injury results via an oxidant pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Endothelin-1 receptor antagonist: effects on endothelin- and cyclosporine-treated mesangial cells.

Endothelin-1 (Et) has profound effects on glomerular microcirculation and mesangial cell contraction. A parameter of mesangial cell contraction was examined by measuring myosin light chain phosphorylation (MLCP) in glomerular mesangial cells in the presence and absence of a newly developed endothelin-1 receptor antagonist (EtA). Addition of Et alone (10 nM) caused a marked increase in MLCP, which, on average, rose by 53 +/- 6% above the level in cells exposed to vehicle (P less than 0.0005). This effect was shown to continue for at least one hour; MLCP at 60 minutes was 64 +/- 12% higher than controls, (P less than 0.025), constituting a unique observation of an in vitro parameter which parallels the characteristic in vivo effect of Et. Treatment of cells with EtA virtually abolished this Et-induced increase in MLCP, which rose by only 2 +/- 3% and -1 +/- 4% for doses of EtA of 44 nM and 66 nM, respectively. Examination of the intracellular calcium concentration, [Ca2+]i, revealed that EtA almost completely abolished the transient increase in [Ca2+]i evoked by Et and also suppressed the early portions of the sustained increase in [Ca2+]i. EtA was ineffective in abolishing [Ca2+]i increase in response to arginine vasopressin. Finally, to evaluate EtA's efficacy in a pathophysiologic setting, we also studied mesangial cells exposed to cyclosporine (Cs). Exposure of mesangial cells to Cs (10(-5) M) for 60 minutes caused a significant increase in MLCP, on average, by 38 +/- 6% above control (P less than 0.0005), while cells exposed to Cs in the presence of EtA increased MLCP significantly less, by only 15 +/- 9%. These data provide further evidence for Et's long-lasting cellular actions, and demonstrate inhibitory effects of an Et receptor antagonist after direct cellular exposure to Et and also after Cs exposure, a pathophysiologic setting which likely involves Et.

Amino Acid Sequence↗
PubMed1992

Different guanosine triphosphate-binding proteins couple vasopressin receptor to phospholipase C and phospholipase A2 in glomerular mesangial cells.

To evaluate the identity of the guanosine triphosphate--binding proteins coupling arginine vasopressin receptor occupancy with activation of phospholipase C, leading to Ca2+ mobilization, and activation of phospholipase A2, leading to arachidonate release and prostanoid formation, we used intact cells, saponin-permeabilized cells, and membranes of the rat mesangial cell. Arginine vasopressin 10(-7) mol/L produced a dose-dependent increase in cytosolic Ca2+ to maximal levels of 500 nmol/L with peak responses occurring within 10 seconds of addition of arginine vasopressin to cells in suspension. Arginine vasopressin 10(-7) mol/L elicited a maximal response. These increases were associated temporarily with a fourfold increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation in prelabeled cells. Pertussis toxin (200 ng/ml) did not inhibit the Ca2+ increase nor did it inhibit the increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation, suggesting a pertussis toxin--insensitive signaling pathway for phospholipase C hydrolysis in response to vasopressin. Membranes prepared from mesangial cells increased D-myo-inositol 1,4,5-trisphosphate formation in vitro in response to arginine vasopressin and guanosine-5'-0(3- thiotrisphosphate), and this stimulation was inhibited by guanosine-5'-0(2-thiodiphosphate), confirming the involvement of a guanosine triphosphate--binding protein. In contrast arginine vasopressin stimulated arachidonate release from intact mesangial cells, and this effect was blocked by pretreating cells with pertussis toxin. To demonstrate that this was through a pertussis toxin--sensitive guanosine triphosphate--binding protein, we permeabilized cells with saponin and determined that arginine vasopressin and guanosine-5'-0(3-thiotriphosphate) stimulated the release of arachidonic acid and the stimulation of guanosine-5'-0(3-thiotriphosphate) was inhibited by guanosine-5'-0(2-thiodiphosphate). Finally, pertussis toxin was able to stimulate adenosine diphosphate ribosylation in vivo of a substrate protein in mesangial cell membranes of 41 kd, and this ribosylation was inhibited by pretreating cells with pertussis toxin. These data suggest that the release of arachidonic acid by vasopressin in glomerular mesangial cells is linked to a pertussis toxin--sensitive guanosine triphosphate--binding protein and that this activation of phospholipase C in vasopressin is linked to a pertussis toxin--insensitive guanosine triphosphate--binding protein.

Adenosine Diphosphate Ribose↗
PubMed1992

Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth.

Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.

Animals↗
PubMed1976

Mesangial cell cytoplasm and glomerular disease.

In this study we have examined mesangial cell cytoplasm as seen by light microscopy of plastic embedded renal biopsy material. An assessment of mesangial cell morphology has been made in each of the 350 renal biopsies, and this has been correlated with the disease process. A surprisingly close correlation with the type of disease present was demonstrated. Thus it appears that an increase in mesangial cell cytoplasm correlates with an active process involving the mesangial area. It is suggested that the index of mesangial cell reactivity may be useful in diagnosis of glomerular disease processes.

Cytoplasm↗
PubMed1992

Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.

Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.

Animals↗
PubMed1992

Human mesangial cells synthesize interleukin 1 alpha but not interleukin 1 beta, interleukin 1 receptor antagonist, or tumour necrosis factor.

There is controversy over whether mesangial cells synthesize and release IL-1 and TNF, and many of the positive experiments were performed before specific reagents and molecular probes were available. Consequently we have stimulated human mesangial cells using protocols known to stimulate the synthesis of other cytokines. No mRNA for IL-1 beta or TNF could be detected in quiescent or proliferating mesangial cells irrespective of whether they had been exposed to cytokines or not. In contrast mRNA for IL-1 alpha was detected in cells stimulated with IL-1 beta 10 ng/ml or with TNF 500 ng/ml; IL-1 alpha was also detected in cell lysates from stimulated mesangial cells. We could not detect mRNA for IL-1 receptor antagonist in any of the cell preparations. These results suggest that mesangial cells are unlikely to be a major source of IL-1 beta or TNF.

Cells, Cultured↗
PubMed1992

Unimpaired formation of hormone-stimulated inositol trisphosphate in human mesangial cells under hyperglycemic conditions.

The relationship between bulk cellular myo-inositol content and phosphatidylinositol metabolism was evaluated in a human mesangial cell line under euglycemic and hyperglycemic conditions. Mesangial cells maintained in high glucose medium displayed a concentration-dependent fall in myo-inositol as measured by gas-liquid chromatography. Measurements of phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate mass revealed slight but statistically insignificant increases in cells exposed to high glucose containing medium. CDP-diacylglycerol: myo-inositol 3-phosphatidylinositol transferase activity, measured in plasma membranes from mesangial cells grown under control and hyperglycemic conditions, was kinetically similar with Michaelis constants (Km values) for myo-inositol of 2.9 and 2.1 mM, respectively. Finally, hormone-stimulated intracellular calcium mobilization and myo-inositol 1,4,5-trisphosphate mass was measured from mesangial cells grown under normal and hyperglycemic conditions. Both intracellular calcium and inositol trisphosphate formation were unchanged in cells previously exposed to high glucose conditions (400 mg/dl) compared to cells grown under normal glucose concentration (100 mg/dl). These data indicate that bulk changes in myo-inositol induced by hyperglycemia are neither associated with alterations in basal levels of inositol containing glycerolipids nor with changes in hormone-stimulated calcium mobilization and inositol trisphosphate formation under conditions of short term changes in extracellular glucose.

Bradykinin↗
PubMed1992

High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-beta.

We investigated the effects of glucose concentration in serum-free media on the proliferative growth response of a cultured murine mesangial cell line. Raising the ambient D-glucose concentration from 100 mg/dl to 450 mg/dl stimulated cell proliferation after 24 to 48 hours but had a growth inhibitory effect after 72 to 96 hours of incubation. This biphasic proliferative response to high glucose concentration was not mediated by the elevated osmolarity of the medium and did not occur when L-glucose was used. The early phase of glucose-induced proliferation was associated with increased expression of the immediate early genes c-myc and egr-1 as well as with induction of the S-phase related proliferating nuclear cell antigen (PCNA). Several lines of evidence indicated that the late phase of glucose-induced growth inhibition was mediated by the bioactivation of endogenous transforming growth factor beta (TGF-beta). Neutralizing antibody against TGF-beta prevented the late inhibitory effects of glucose on proliferation. On the other hand, exogenous TGF-beta (1 ng/ml) significantly inhibited basal proliferation in mesangial cells. Furthermore, Northern blot analysis revealed that TGF-beta 1 mRNA was induced by 450 mg/dl glucose in the medium after 48 to 72 hours, but not after 24 hours. Cell cycle analysis demonstrated that mesangial cells incubated in high glucose for 24 hours have a higher percentage of cells in the S-G2 phase of the cell cycle compared with cells grown in normal glucose concentration. After 48 hours of culture in elevated glucose concentration, the percentage of cells in S-G2 phase was decreased, and became comparable to that of cells in normal glucose concentration. However, the addition of neutralizing anti-TGF-beta antibody stimulated the progression of cells towards S-G2 in high glucose medium after 48 hours. The findings of this study demonstrate a biphasic growth response of mesangial cells when they were cultured in high glucose concentration; initially there was a transient stimulation of replication for 24 to 48 hours followed by a sustained inhibition after longer incubation periods. This inhibition may be mediated by the glucose-induced synthesis and/or bioactivation of TGF-beta which can inhibit proliferation of mesangial cells in an autocrine fashion.

Animals↗
PubMed1992

Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells.

Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.

Aluminum↗
PubMed1992

Specific receptors for beta-endorphin on mesangial cells.

beta-Endorphin is an endogenous opioid considered to be a modulator of immune injury. We studied the binding of [125I]beta-endorphin on cultured rat mesangial cells at 4 and 37 degrees C. The results were analyzed by computer program (Ligand). Incubation of rat mesangial cells with unlabeled beta-endorphin displaced [125I]beta-endorphin in a concentration-dependent manner. The binding of [125I]beta-endorphin was not affected by either opiate agonists or antagonists. Saturation studies at 37 degrees C revealed that beta-endorphin binding was time dependent. Binding studies revealed the presence of a single class of high-affinity binding sites with an apparent Kd of 15.3 nM. The number of receptor sites was calculated as 8.48 x 10(5) sites/cell. Mesangial cells exposed to beta-endorphin (10(-6) M) for 48 h showed enhanced incorporation of [3H]thymidine when compared to untreated cells (control, 23,228 +/- 2,778 cpm/well vs. beta-endorphin, 44,887 +/- 4,259 cpm/well; p less than 0.01). Our results show that mesangial cells carry a specific receptor for beta-endorphin which may be linked to proliferation of mesangial cells.

Animals↗
PubMed1978

Relationship between glomerular mesangial cell proliferation and amyloid deposition as seen by ultrastructural and morphometric analysis in experimental kala-azar of the hamster.

Light and electron microscopic studies combined with a morphometric analysis of the hamster glomerulus in experimental kala-azar showed progressive hyperplasia of mesangial cells beginning on the 10th day and reaching a peak on the 20th day after infection. Afterward, the number of mesangial cells declined and a progressive rise of amyloid deposits over the mesangial matrix was observed. This system for amyloid production is unique if we consider that probably one cell, the mesangial cell, is involved in glomerular amyloid deposition. Our data support a slight modification in the sequence of events of the biphasic theory of amyloid formation. We observed that the number of mesangial cells declines when amyloid deposition increases and that mesangial cell morphology in this stage is not that of an actively secreting cell. It is therefore hypothesized that amyloid precursor material is secreted into the matrix during the proliferative phase. In the second phase, amyloid deposits occur in the extracellular media close to functionally impaired mesangial cells.

Amyloid↗