Fibrillary glomerulonephritis and immunotactoid glomerulopathy: two entities, not one.
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Glomerulonephritis↗
Biomedical subjects
C E Alpers
Publications and source records attributed to C E Alpers.
De novo amyloidosis in a renal allograft: a case report and review of the literature.
Recurrent amyloidosis is an uncommon but well-documented event in up to 26% of renal allograft recipients transplanted for amyloid renal disease. Both primary and secondary amyloidoses recur. De novo primary and secondary amyloid have not been previously reported. We report the first occurrence of de novo secondary amyloid in a renal allograft recipient. The cause of the secondary amyloidosis is unproven, but possible etiologies include inflammation secondary to occult hepatitis, rheumatoid arthritis, or chronic rejection. Colchicine therapy has not resulted in decreased proteinuria or improved renal function.
Amyloid↗
Expression of vascular cell adhesion molecule-1 in kidney allograft rejection.
VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial cells in culture, may mediate mononuclear leukocyte infiltration in vessels and interstitium in solid organ allograft rejection. Using the avidin-biotin immunoperoxidase technique and an affinity-purified rabbit polyclonal antisera to recombinant human VCAM (rVCAM Ab) which works in methyl Carnoy's fixed tissues, we studied the expression of this molecule in biopsies of transplanted kidneys (N = 34) with and without features of rejection and allograft nephrectomies (N = 17) as well as nontransplanted control tissues (N = 26). The rVCAM Ab showed a population of reactive endothelial cells limited to sites of prominent subendothelial leukocytic cell infiltration in arteries and veins, and occasional peritubular capillaries (PTC) in rejecting allografts. Endothelial expression of VCAM was rarely identified in biopsies showing interstitial rejection only or cyclosporine toxicity, usually in PTC, and was only rarely encountered in nontransplanted control tissues. Apparent de novo expression of VCAM-1 by arterial smooth muscle cells and mesangial cells was present in cases of severe rejection. In addition, a population of cells (DC) with dendritic morphology was identified by rVCAM Ab within sites of lymphoid cell aggregation in rejecting allografts. Further evidence that these cells represent true DC was obtained by identification of VCAM-1 positive, morphologically similar cells in both germinal centers and interfollicular areas of all seven reactive lymph nodes tested; and by similar staining of these cells in the allografts and lymph nodes by antibodies to nerve growth factor receptor and the complement receptor CR1, previously shown to recognize DC. DCs were generally not seen in uninflamed normal control organs or portions of allografts uninvolved by lymphoid aggregates. Enhanced tubular epithelial cell expression of VCAM-1 was also present in rejecting allografts. All staining could be abolished by absorption of the antisera with VCAM-1 transfected, but not ICAM-1 or ELAM-1 transfected, CHO cells. In situ hybridization studies utilizing a cDNA probe to human VCAM-1 demonstrated mRNA production by glomerular, tubular and vascular cells corresponding to sites where the protein was immunohistochemically localized.(ABSTRACT TRUNCATED AT 400 WORDS)
Arteries↗
PDGF-receptor localizes to mesangial, parietal epithelial, and interstitial cells in human and primate kidneys.
There is evidence that platelet derived growth factor (PDGF) is a mediator of proliferative changes in renal arteries and mesangium in human disease, in the mesangium in experimental mesangial proliferative glomerulonephritis, and in the interstitium in a rodent model of angiotensin II mediated hypertension. We utilized a monoclonal antibody to the beta-subunit of the PDGF-receptor to localize constitutive expression of this receptor in human and nonhuman primate tissues. Tissues were fixed in cold 2 or 4% paraformaldehyde, and immunohistochemical techniques both at the light microscopic level and immunoelectron microscopy were employed. In the glomerulus, there is widespread expression of this molecule by mesangial cells, and there is frequent expression on the apical and lateral surface of parietal epithelial cells. There is also widespread expression of this molecule by cortical and medullary peritubular interstitial cells, but not by glomerular or peritubular capillary endothelium or other renal parenchymal structures. The identification of receptors capable of binding PDGF B-chain at each of these sites: (1) provides a basis for PDGF mediated mesangial proliferation in human disease; (2) provides a basis for PDGF mediated interstitial cell migration and/or proliferation and/or activation at sites of tubulointerstitial injury; and (3) suggests that glomerular parietal epithelial cells may be responsive to stimulation by PDGF.
Animals↗
Proliferation in primary and restenotic coronary atherectomy tissue. Implications for antiproliferative therapy.
On the basis of animal models of arterial injury, smooth muscle cell proliferation has been posited as a dominant event in restenosis. Unfortunately, little is known about this proliferation in the human restenotic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary atherectomy-derived tissue. Primary (n = 118) and restenotic (n = 100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The identity of PCNA-positive cells was then determined using immunohistochemical cell-specific markers. Eighty-two percent of primary specimens and 74% of restenotic specimens had no evidence of PCNA labeling. The majority of the remaining specimens had only a modest number of PCNA-positive cells per slide (typically < 50 cells per slide). In the restenotic specimens, PCNA labeling was detected over a wide time interval after the initial procedure (eg, 1 to 390 days), with no obvious proliferative peak. Cell-specific immunohistochemical markers identified primary and restenotic PCNA-positive cells as smooth muscle cells, macrophages, and endothelial cells. In conclusion, the findings were as follows: (1) Proliferation in primary and restenotic coronary atherectomy specimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angioplasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explain why current approaches to restenosis therapy have been ineffective.
Adult↗
Carotid artery intraplaque hemorrhage and stenotic velocity.
BACKGROUND AND PURPOSE: One of the proposed mechanisms for sudden expansion of a carotid bifurcation plaque is hemorrhage within the lesion. It has been postulated that the sudden increase in plaque size will acutely reduce blood flow to the ipsilateral hemisphere and induce either a transient ischemic attack or a stroke. In this study, the relation between peak systolic velocity at the site of narrowing and its potential role in the development of intraplaque hemorrhage were investigated. METHODS: Ten patients who had carotid endarterectomy were examined by duplex Doppler sonography before surgery to determine the peak systolic velocity at the site of maximal narrowing. The excised carotid plaques were sectioned at 1-mm intervals and examined for histological evidence of intraplaque hemorrhage. The recorded peak systolic velocities in patients with intraplaque hemorrhage were compared with the velocities in cases in which no hemorrhage was identified. RESULTS: Five of the ten patients had intraplaque hemorrhage. Four of the five patients with intraplaque hemorrhage had a peak systolic velocity of > 420 cm/sec and diastolic velocities of > 160 cm/sec; none of the patients without intraplaque hemorrhage had such high values. CONCLUSIONS: Peak systolic velocity is significantly higher in patients with intraplaque hemorrhage. The specificity and sensitivity of a peak systolic velocity of > 420 cm/sec in predicting intraplaque hemorrhage remains to be determined.
Arteriosclerosis↗
Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques.
In an earlier report, we used differential cloning to identify genes that might be critical in controlling arterial neointima formation (Giachelli, C., N. Bae, D. Lombardi, M. Majesky, and S. Schwartz. 1991. Biochem. Biophys. Res. Commun. 177:867-873). In this study, we sequenced the complete cDNA and conclusively identified one of these genes, 2B7, as rat osteopontin. Using immunochemistry and in situ hybridization, we found that medial smooth muscle cells (SMC) in uninjured arteries contained very low levels of osteopontin protein and mRNA. Injury to either the adult rat aorta or carotid artery using a balloon catheter initiated a qualitatively similar time-dependent increase in both osteopontin protein and mRNA in arterial SMC. Expression was transient and highly localized to neointimal SMC during the proliferative and migratory phases of arterial injury, suggesting a possible role for osteopontin in these processes. In vitro, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), and angiotensin II (AII), all proteins implicated in the rat arterial injury response, elevated osteopontin expression in confluent vascular SMC. Finally, we found that osteopontin was a novel component of the human atherosclerotic plaque found most strikingly associated with calcified deposits. These data implicate osteopontin as a potentially important mediator of arterial neointima formation as well as dystrophic calcification that often accompanies this process.
Amino Acid Sequence↗
Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats.
Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.
Animals↗
Role of platelet-derived growth factor in glomerular disease.
An approach for establishing a role for a growth factor in glomerular disease is presented. Using platelet-derived growth factor (PDGF) as an example, there is strong evidence to support the hypothesis that PDGF is a mediator of mesangial cell proliferation in glomerulonephritis. This includes evidence that (1) PDGF is a mitogen for mesangial cells in culture; (2) PDGF is expressed in both experimental and human glomerulonephritis in which mesangial cell proliferation occurs; (3) infusion of PDGF into rats induces mesangial cell proliferation and a hypercellular lesion; and (4) inhibition of PDGF in a model of experimental nephritis significantly reduces the mesangial cell proliferation. However, these data do not answer the question of whether or not the inhibition of PDGF in human diseases would be beneficial in the long term, because some cell proliferation is likely required for normal healing and repair. Further studies will be necessary to resolve this issue.
Animals↗
Expression of vascular cell adhesion molecule (VCAM-1) in liver and pancreas allograft rejection.
VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial cells in culture, may mediate mononuclear leukocyte infiltration in vessels and interstitium in solid organ allograft rejection. Using the avidin-biotin immunoperoxidase technique and two different antibodies--4B9, a murine monoclonal antibody, and rabbit polyclonal antisera to recombinant human VCAM (rVCAM Ab), which work in methacarn-fixed tissues--we studied the expression of this molecule in biopsies of transplanted liver and pancreas with and without features of rejection as well as nontransplant control tissues. The rVCAM Ab, but not 4B9, showed a population of reactive endothelial cells limited to sites of prominent subendothelial leukocytic cell infiltration in arteries and veins in rejecting allografts. VCAM-1 expression by sinusoidal endothelium in rejecting liver allografts was also observed. In addition, a population of cells (DC) with dendritic morphology was identified by rVCAM Ab within sites of lymphoid cell aggregations in both liver and pancreas allografts. Further evidence that these cells represent true DC was obtained by identification of VCAM-1 positive morphologically similar cells in both germinal centers and interfollicular areas of reactive lymph nodes; and by similar staining of these cells in allograft organs by a monoclonal antibody to nerve growth factor receptor, previously shown to recognize DC. DCs were generally not seen in normal control organs or portions of allografts uninvolved by lymphoid aggregates. This study provides evidence that 1) endothelial cell expression of VCAM-1 may be important in transplant rejection, 2) different epitopes of VCAM-1 may be preserved in tissue sections and recognized by different antibodies, and 3) there is probably a population of VCAM-1 expressing DC that participates in the cellular rejection progress.
Antibodies, Monoclonal↗
Nerve growth factor receptor expression in fetal, mature, and diseased human kidneys.
BACKGROUND: Nerve growth factor (NGF) has been proposed to be critical to normal renal development in rodents. However, little is known about expression of NGF or its receptors in human kidneys, or their potential function in development or disease. EXPERIMENTAL DESIGN: A previously characterized monoclonal antibody (NGFR 5) was utilized for immunohistochemical localization of the p75 NGF receptor (NGFR) in alcohol-fixed tissue sections of human fetal kidney (N = 27, 54 to 105 days gestation), normal mature kidney obtained from nephrectomies for neoplasia (N = 7), and renal biopsies (N = 54) with various glomerulopathies previously characterized for degree of mesangial alpha smooth muscle actin (alpha SM) expression. A second monoclonal antibody (NGFR2) was also utilized on fetal and normal kidney. Immunohistochemical localization of alpha SM and proliferating cell nuclear antigen expression was also performed. RESULTS: Glomerular expression of NGFR in the fetus is limited to the mesangium in later stages of glomerulogenesis; at these stages this expression is similar to that which has been previously reported for platelet-derived growth factor receptor-beta and alpha SM. There is focal, weak persistence of NGFR in normal adult glomeruli, similar to alpha SM. In renal biopsies, glomerular NGFR expression was upregulated in a variety of disease states, which frequently but not invariably correlated with alpha SM expression. Fetal and adult expression of NGFR is also prominent in periarterial connective tissue cells and nerve. Apparent de novo expression by many interstitial cells in normal and diseased adult kidneys is also present. CONCLUSIONS: These studies indicate: (a) NGF or other neurotrophins that bind NGFR may be important in human kidney development and glomerular response to injury; (b) NGFR is a marker of developing mesangial cells similar to alpha SM and platelet-derived growth factor receptor-beta; (c) enhanced expression of NGFR, like alpha SM, is a marker of mesangial cell injury or activation, and that their coordinate upregulation in some glomerular disease states appears to recapitulate a normal developmental state; (d) a population of NGFR and platelet-derived growth factor-beta expressing interstitial cells can be identified in normal kidneys, which suggests potential signaling mechanisms to recruit or activate these cells at sites of tubulointerstitial injury.
Antibodies, Monoclonal↗
Visceral glomerular epithelial cells can proliferate in vivo and synthesize platelet-derived growth factor B-chain.
In glomerular diseases associated with antibody- and complement-mediated injury to endothelial and mesangial cells, cell proliferation is an important early response that precedes matrix accumulation and glomerulosclerosis. In contrast, in diseases in which the visceral glomerular epithelial cell (vGEC) is the principal target of injury, cell proliferation is not a recognized consequence, although vGECs respond in vitro to a variety of growth factors and inflammatory mediators. To explore the possibility that low levels of vGEC proliferation may occur and participate in such diseases, serial studies were done in the passive Heymann nephritis model of membranous nephropathy, in which the vGEC is the primary target of antibody- and C5b-9-mediated injury. The results showed mitotic figures and positive staining for the proliferating cell nuclear antigen in cells whose location defined them as vGECs. The proliferating cell nuclear antigen-positive cells at the edge of the capillary wall were confirmed to be vGECs by double-immunostaining with antibodies to SPARC/osteonectin, which preferentially label vGECs in passive Heymann nephritis. Proliferation of vGECs in vivo was preceded by increased glomerular expression of platelet-derived growth factor (PDGF) B-chain protein and messenger RNA, both of which localized to vGECs. PDGF B-chain protein and messenger RNA were also detected in cultured vGECs. PDGF receptor beta-subunit protein or messenger RNA could not be demonstrated in vGECs in vivo or in vitro, and no growth response of cultured vGECs to PDGF was noted. These results suggest that proliferation of vGECs does occur in a model of glomerular injury induced by antibody and C5b-9 on vGECs. VGEC proliferation and production of PDGF may be involved in the restoration of the capillary wall but could also contribute to local capillary wall injury and proliferation of other cells in Bowman's capsule, interstitium, and tubules.
Animals↗
Human mesangial cells are resistant to productive infection by multiple strains of human immunodeficiency virus types 1 and 2.
Human immunodeficiency virus-associated nephropathy (HIVAN) is a recognized clinical entity of unknown pathogenesis. A role for viral infection of renal cells in the initiation of this process at present is an intriguing but untested hypothesis. Studies in primate models of acquired immunodeficiency syndrome (AIDS) suggest that injury to the mesangial cell may be central to the sclerosing glomerular lesion characteristic of HIVAN. We therefore tested the infectibility of human mesangial cells (HMC) in vitro by a variety of strains of HIV chosen to include a spectrum of tropisms for different cell types. Productive infection of mesangial cells could not be demonstrated using any of the virus strains. Nonetheless, HIV infection of intrinsic renal cells remains an attractive area of inquiry for understanding the natural history of HIVAN.
AIDS-Associated Nephropathy↗
Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis?
Immunotactoid glomerulopathy (IT), or alternatively, microtubular glomerulopathy, is a term that has been used by some investigators to encompass those glomerulopathies characterized by the presence of fibrillar or microtubular deposits which are distinguished from amyloid principally by their larger size and lack of reactivity with the Congo red reagent. A case is presented here of IT as it was initially described. The present case, and a review of the literature, suggest that the diagnosis of IT be restricted to those glomerulopathies associated with large, at times organized, microtubular deposits. Terms such as fibrillary glomerulonephritis, or alternatively Congo red-negative amyloidosis-like glomerulopathy, could then be used to describe those patients with smaller, fibrillar glomerular deposits having an appearance closely resembling amyloid. We believe it is possible to separate the entities fibrillary glomerulonephritis and IT on morphological grounds. This is a potentially useful distinction that identifies patients who are likely to have or develop clinical evidence of a lymphoplasmacytic disorder or dysproteinemia, which are associated with deposits of IT, and distinguishes them from patients with fibrillary glomerulonephritis, of whom only a single case has been linked to such clinical findings.
Biopsy↗
Enhanced expression of "muscle-specific" actin in glomerulonephritis.
Increased expression of "muscle-specific" actin can be correlated with mesangial cell injury and proliferation in the rat. We performed similar immunohistochemical studies using two monoclonal antibodies (MoAb) to "muscle-specific" actins (HHF-35, a MoAb to pan muscle actin and alpha-SM-1, a MoAb to alpha-smooth muscle actin) on methyl Carnoy's fixed human renal biopsies which demonstrated a wide variety of inflammatory, proliferative, and non-proliferative glomerular diseases. Most glomerular diseases were associated with increased "smooth-muscle" actin expression. Exceptions almost invariably were disease settings without prominent cellular proliferation. As in the rat, there was a correlation of induced actin expression with increased glomerular cell proliferation, as detected by staining with a MoAb to proliferating cell nuclear antigen (PCNA). Double immunolabeling studies with an antibody to the leukocyte common antigen showed the great majority of PCNA+ proliferating cells to be intrinsic glomerular cells rather than infiltrating leukocytes. These studies demonstrate that phenotypic changes of mesangial cells occur in both human and experimental glomerulonephritis, and are identifiable in fixed tissue sections. These studies also suggest that markers of mesangial cell injury or activation and proliferation, such as immunostaining of renal biopsies for "muscle-specific" actins, might be useful diagnostic and/or prognostic indicators in proliferative or sclerosing glomerular diseases.
Actins↗
Developmental patterns of PDGF B-chain, PDGF-receptor, and alpha-actin expression in human glomerulogenesis.
Expression of PDGF B-chain and the PDGF receptor beta-subunit (PDGFR beta) is detected immunocytochemically during the development of glomeruli in human kidneys of 54 to 105 days gestational age. During the early stages (vesicular, comma-shape and S-shape) of glomerulogenesis, PDGF B-chain is localized to differentiating epithelium of the glomerular vesicle, while PDGFR beta is expressed in the undifferentiated metanephric blastema, vascular structures, and interstitial cells. During this stage PDGF may be acting as a paracrine growth factor and as a chemoattractant acting to recruit mesangial progenitor cells into the developing glomerulus. As the glomerular tuft forms, both PDGF B-chain and PDGFR beta can be detected in an arboreal pattern radiating from the hilus of the glomerular tuft. Immunocytochemical studies using markers specific to endothelium (Ulex europaeus I lectin, Factor VIII related antigen), and smooth muscle (alpha-smooth muscle actin), indicate that the PDGF B-chain and PDGFR beta are both expressed primarily by mesangial cells. During this stage, PDGF may be acting primarily to provide an autocrine factor to mediate further mesangial cell proliferation. Glomerular expression of alpha-smooth muscle actin is limited to later stages of glomerulogenesis; at these stages the pattern of expression is similar to that of PDGF-B chain and PDGFR beta. The upregulation of mesangial PDGF, PDGFR beta, and alpha-smooth muscle actin expression that has been identified in some disease states in both humans and experimental animals appears to represent a recapitulation of this normal developmental process.
Actins↗
Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy.
Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.
Animals↗
Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model.
Increasing evidence supports a role of glomerular cell proliferation in the development of focal or diffuse glomerulosclerosis. This study investigates the chronology and sequence of cellular events that precede glomerulosclerosis in 5/6 nephrectomized rats. Within three days of renal ablation, a phenotypic switch occurred in which some mesangial cells expressed alpha-smooth muscle actin. This was followed by proliferation of mesangial cells, and to a lesser degree endothelial cells from day 5 to week 4 as detected by immunostaining for the proliferating cell nuclear antigen (PCNA). Glomerular cell proliferation was accompanied by increased immunohistochemical expression of PDGF B-chain. In situ hybridization showed no glomerular PDGF B-chain mRNA expression at the induction of proliferation (day 5), and a marked increase between week 1 and 4 in operated rats. In parallel, increased expression of PDGF receptor beta-subunit protein and mRNA was demonstrated by immunohistochemistry and Northern analysis of total glomerular RNA. The onset of glomerular cell proliferation was also associated with mild glomerular platelet accumulation (as defined by 111In-labelled platelet studies) as well as with fibrinogen deposition. Proteinuria, glomerular sclerotic changes, and leukocyte infiltration all followed cell proliferation. The glomerular leukocyte infiltrate consisted of monocytes/macrophages and increased markedly at week 10 in rats with renal ablation. Thus, our results suggest that in the remnant kidney model: 1) proliferation of intrinsic glomerular cells precedes glomerulosclerosis; 2) proliferation may be initiated by degranulating platelets and sustained by PDGF released from intrinsic glomerular cells; and 3) glomerular monocyte/macrophage infiltration occurs after the proliferation, and may possibly contribute to the development of glomerular sclerotic changes.
Actins↗