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PubMed1996

An experimental model for acute poststreptococcal glomerulonephritis in mice.

A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis-associated strain induced hypercellularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non-nephritis-associated strain and non-infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.

Animals↗
PubMed2003

[Henoch-Schönlein purpura - one of the most common types of systemic vasculitis in childhood].

UNLABELLED: The aim of our study was to estimate etiology, most common clinical findings, the course and peculiarities of treatment in children to whom Henoch-Schönlein purpura was diagnosed during 1996-2002 at Clinic of Children's Diseases of Kaunas University of Medicine Hospital. METHODS: The Henoch-Schönlein purpura diagnosis was based on the association of non-trombocytopenic purpura, arthritis and abdominal pain in 45 children, mostly at preschool age. Routine laboratory blood tests usually were normal. Serum level of imunoglobulin A (Ig A), complement 3, 4 (C(3), C(4)), antineutrophil cytoplasm antibodies were measured for some patients. Urinary analyses were performed for all patients in order to assess nephritis. RESULTS: In 1/3 (33.3%) of children Henoch-Schönlein purpura was preceded by an upper respiratory tract infection. The most common clinical signs were: non-trombocytopenic purpura -100%, subcutaneous edema - 53%, arthritis of large joints - 64%, gastrointestinal symptoms (pain, diarrhea with bleeding) - 37.5%. The incidence of renal involvement was 13.3%, but usually not at the onset of the disease. Relapses were often, and they had tendency to repeat in 1-2 week periods. Late relapses were absent. Treatment of Henoch-Schönlein purpura was symptomic. Nonsteroidal anti-inflammatory drugs which are helpful in joint pain, were prescribed for 33.3% patients. Steroids which reduce abdominal pain, melena, massive hemorrhage, nephritic symptoms, were given for 28.8% patients. CONCLUSIONS: Non-trombocytopenic purpura, arthritis and colic abdominal pain, classic triad of Henoch-Schönlein purpura that occurs in early stage of the disease, were most common. Renal involvement had tendency occur later. Nonsteroidal anti-inflammatory drugs were prescribed for patients with arthritis; prednisone reduced gastrointestinal, nephritic symptoms. Relapses were often.

Adolescent↗
PubMedDate not supplied

AT1-receptor antagonists abolish glomerular MCP-1 expression in a model of mesangial proliferative glomerulonephritis.

BACKGROUND: Glomerular accumulation of macrophages/monocytes (M/M) is a typical early feature in the course of anti-thymocyte serum (ATS)-induced nephritis. We have previously shown that glomerular synthesis and expression of monocyte-chemoattractant protein-1 (MCP-1) occurs before influx of M/M and a neutralizing anti-MCP-1 antibody reduced this cell infiltrate by one third. The present study was undertaken to test the effect of two angiotensin II type 1 (AT1) receptor antagonists, losartan and irbesartan, on ATS-stimulated MCP-1 expression as well as glomerular influx of M/M. METHODS: Treatment of rats with either losartan or irbesartan was started 24 h before administration of ATS. After 24 h, MCP-1 mRNA expression was evaluated by RT-PCR and Northern blots. MCP-1 protein was determined by Western blots and chemotactic factors released from isolated glomeruli were measured by chemotactic assay. Kidney sections were stained for rabbit IgG, complement C3, and M/M (ED1 antigen). RESULTS: Both AT1-receptor antagonists caused a significant, but not total reduction in MCP-1 mRNA and protein expression 24 h after injection of ATS. Treatment with losartan or irbesartan also reduced the chemotactic activity of isolated glomeruli from nephritic animals. Quantification of ED1-positive cells revealed that losartan as well as irbesartan reduced glomerular M/M invagination in nephritic rats by approximately 30-50%. However, treatment with AT1-receptor antagonists did not influence binding of ATS to mesangial cells and subsequent complement activation indicating that the attenuated MCP-1 expression is not due to differences in delivery and binding of ATS to mesangial cells. CONCLUSION: Our data indicate that short-term antagonism of AT1 receptors abolished the early glomerular MCP-1 expression and M/M influx. These results indicate that angiotensin II may exert immunomodulatory effects in vivo and adds a new mechanism showing how this vasopeptide may be involved in the pathogenesis of renal diseases.

Angiotensin Receptor Antagonists↗
PubMed2002

Angiotensin II infusion ameliorates the early phase of a mesangioproliferative glomerulonephritis.

BACKGROUND: Inhibition of the renin-angiotensin system slows the progression of chronic renal disease. METHODS: To test whether angiotensin II (Ang II) infusion aggravates or ameliorates an acute glomerulonephritis, the peptide was infused (200 ng/min by osmotic minipump) in rats with an anti-thymocyte antibody-induced glomerulonephritis (ATS). RESULTS: Ang II significantly increased blood pressure. Following injection of the antibody, similar glomerular binding of rabbit IgG and rat complement C3 was detected in ATS and Ang II+ATS rats, indicating no differences in delivery and binding of the antibody. Ang II infusion, however, induced a significant reduction in glomerular monocyte infiltration, cell proliferation and matrix expansion in nephritic rats compared to rats with nephritis without Ang II. The antiproliferative effect of Ang II was inhibited by the Ang II type 1 (AT1) receptor blocker irbesartan, but not by the AT2 receptor blocker PD 123319, indicating that this effect was likely transduced by AT1 receptors. Norepinephrine infusion (600 ng/min) produced a similar degree of hypertension, but did not affect glomerular proliferation in nephritic rats. Ang II induced the glomerular expression of the cell cycle inhibitor p27KIP1 and of transforming growth factor-beta (TGF-beta) and inhibited expression of monocyte chemotactic protein 1 (MCP-1). CONCLUSION: Ang II surprisingly ameliorates glomerular monocyte infiltration, proliferation and matrix expansion in ATS nephritis. Ang II-mediated induction of cyclin kinase inhibitors and TGF-beta may contribute to the protection of the glomerulus from inflammatory injury by inducing cell cycle arrest and attenuating activation of local and recruited cells. Alternatively, Ang II might protect the kidney at least in part by less inflow of disease activators due to reduction of renal blood flow. Therefore, activation of the renin-angiotensin system may have protective effects in certain pathophysiological situations.

Angiotensin II↗
PubMed2005

IgG naturally occurring antibodies stabilize and promote the generation of the alternative complement pathway C3 convertase.

Normal human IgG contains naturally occurring anti-C3 antibodies (anti-C3 NAbs) that have been proposed to regulate complement amplification. Here, we report a novel procedure for anti-C3 NAb purification. Pooled human IgG was fractionated on a DEAE column prior to affinity chromatography on IgG and then on C3. Anti-C3 NAbs co-purified with anti-F(ab')2 NAbs. In a refined protocol, IgG fractions were absorbed on Fc, F(ab')2, and C3, which allowed to isolate the directly accessible NAbs and to remove IgG hinge-region-specific NAbs. Since a substantial fraction of total anti-C3 NAbs in whole IgG pre-existed as complexes, IgG that did not bind to the three affinity columns was treated with urea and the affinity chromatography repeated to collect the dissociated NAbs. The urea-accessible anti-F(ab')2 NAbs were rather pure but anti-C3 NAbs yet contained substantial amounts of anti-F(ab')2 NAbs. Anti-C3 NAbs showed up to 400-fold and anti-F(ab')2 NAbs, up to 30-fold enrichment as compared to pooled normal human IgG. Anti-C3 NAb preparations exhibited nephritic factor activity that was up to 60 times stronger than that of total IgG from a patient with membranoproliferative glomerulonephritis type 2. In addition, anti-C3 NAbs promoted C3 convertase generation, when added to the convertase precursor or during convertase assembly, suggesting a non-nephritic-factor mechanism. Factors H and I reduced the overall level of activity but had no influence on the NAb dose-response curve meaning that NAbs did not interfere with factor H binding. Convertase promoting activity during assembly correlated with the content of anti-C3 NAbs in NAb complexes. In conclusion, anti-C3 NAbs associated with framework-specific anti-idiotypic NAbs stabilize C3 convertase and promote its generation but their activity is compensated for in whole IgG.

Antibodies, Anti-Idiotypic↗
PubMed1976

Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function.

A novel component of the properdin system has been discribed which represents a heretofore unrecognized human serum protein. The protein has been tentatively termed the initiating factor (IF) because it functions in the initial reaction of the properdin pathway. IF is a 170,000 dalton beta-pseudoglobulin which is composed of two presumably identical 85,000 dalton chains linked by disulfide bonds. The protein reacts with antibody to nephritic factor, which is defined by its activity and is found in the serum of patients with certain nephritides. The activity of IF is heat stable. Upon treatment of serum with activators of the alternative pathway, the initial C3 convertase is assembled from IF, Factors D and C, C3, and magnesium without participation of properdin. It is the function of the enzyme to deposit C3b on the surface of the activator particles, thereby affording generation of the solid phase enzymes of the pathway, a process that is a prerequisite for properdin activation. By exposure to low pH, IF assumed the electrophoretic mobility of psi-globulin and acquired the ability to generate without activators a fluid phase C3 convertase in serum. Serum depleted of IF did not allow activation of the properdin pathway. Serum depleted of properdin did permit activation of the pathway and expression of cytolytic activity. These results raise the possibility that IF represents the recognition unit of the pathway.

Animals↗
PubMed1985

Hageman factor in experimental nephrotoxic nephritis in the rabbit.

This study was performed to investigate whether the Hageman factor (HF) system might contribute to glomerular damage in vivo. HF was purified from rabbit plasma. The proteolytic activation pattern of 80,000-dalton rabbit HF was the same as that previously reported for human HF. Anti-HF IgG, raised in a goat, was monospecific as judged by immunodiffusion analysis and inhibited HF activity in rabbit plasma. A telescoped model of nephrotoxic nephritis in the rabbit was developed using guinea pig antirabbit glomerular basement membrane IgG injected into rabbits preimmunized against guinea pig IgG. In this model protein excretion was increased by days 3 to 4 in association with glomerular influx of acute inflammatory cells. By days 5 and 6 fibrin was present within glomerular capillaries, beneath endothelial cells, in Bowman's space, and in proximal tubules. By fluorescent microscopic analysis rabbit IgG and C3 had accumulated along the glomerular capillary wall; however, no HF was detectable in glomerular capillary wall over the initial 10 days of glomerular injury. Positive fluorescence for HF was seen within Bowman's space and in tubules along with albumin and plasmin- and fibrin-related antigens. Although the circulating antigenic HF concentration did not change during the glomerular injury, the rate of turnover of 125I-HF did increase. However, when this was factored for turnover of 131I-albumin in a paired study, the relative turnover of 131I-albumin was found to be faster than that of 125I-HF. Proteolysis of 125I-HF in plasma consistent with HF activation was noted in only one of these rabbits in spite of a decrease in antigenic C3 level to 54% of baseline. The 125I-HF appearing in urine of nephritic rabbits had undergone proteolysis from the native 80,000-dalton parent molecule to form fragments of 50,000 and 30,000 daltons, compatible with HF activation. Urine from nephritic rabbits also contained procoagulant activity that was HF dependent. These results are compatible with the concept that HF passively crosses the damaged glomerular filter where it may become activated in Bowman's space or in fluid draining damaged glomeruli in this model of nephrotoxic nephritis in the rabbit.

Animals↗
PubMedDate not supplied

An IgG autoantibody which inactivates C1-inhibitor.

Antibodies are considered to play a specific pathogenic role in certain disease states such as myasthenia gravis, Graves' disease and autoimmune haemolytic anaemia. Autoantibodies which interfere with the function of enzyme cascade systems have also been described in diseases such as acquired haemophilia (anti-factor VIII antibodies) and glomerulonephritis (C3 nephritic factor). The identification of these autoantibodies is crucial to an understanding of the aetiology of such diseases and is also of importance in revealing the inter-relationships of the immune system with other biological pathways. This is the first report of an immunoglobulin G (IgG) autoantibody reactive with C1-inhibitor (C1-Inh), a pivotal inhibitor of the inflammatory response which is known to inactivate proteins of the complement, kinin, fibrinolytic and 'contact phase' systems. This autoantibody was isolated from a patient with a novel variant of acquired angioedema and C1-Inh dysfunction. This finding highlights the involvement of the immune system in the pathogenesis of disorders characterized by the presence of dysfunctional inflammatory response proteins.

Autoantibodies↗
PubMed1977

[Hyperacute rejection of an HL-A identical renal allograft (author's transl)].

Hyperacute renal allograft rejection is described in a patient suffering from mesangio-proliferative glomerulonephritis. The transplanted kidney was HL-A identical and the direct cytotoxic cross-match between the recipient's serum and donor lymphocytes was negative. Intrarenal consumption of C 3, but not of C 1 q, C 4, total haemolytic complement, IgG or Igm was demonstrated. Immunofluorescence studies exhibited dense granular deposits of C 3, but not of IgG, IgM C 1q or C 4. These findings together with the observation of beta 1 C-beta 1A converting activity in the patient's serum, raised the possibility that the alternative pathway of complement activation induced by nephritic factor could have operated in this case. Further studies will be necessary to clarify the question whether hyperacute rejection of renal allografts is only antibody mediated or not.

Acute Disease↗
PubMed1980

The interaction of C5 with C3b in free solution: a sufficient condition for cleavage by a fluid phase C3/C5 convertase.

We have measured the interactions of C3b with C5 in free solution under conditions that favor detecting weak binding interactions (high C3b and low C5 concentrations and low ionic strength). When a mixture of 125I-C5 (2 X 10(-8) M) and unlabeled C3b (3.8 x 10(-5) M) was ultracentrifuged in a sucrose gradient, virtually all of the C5 sedimented to the position of a 13 to 14S complex. In contrast, a sedimentation rate for C5 of 9S was obtained in the absence of C3b. The ability to bind C5 was observed to be a property of C3b since native C3 was unable to bind C5. It was also found that beta 1H by itself could inhibit the binding of C5 to cell-bound C3b. From inhibition studies, we estimate that the association constant for the C3b-C5 interaction is on the order of 2 x 10(6) M-1 in a low ionic strength buffer (mu = 0.06) and 5-fold weaker at physiologic ionic strength. C5 bound to C3b in free solution was cleaved by nephritic factor-stabilized fluid phase C3bB. C5 activation did not occur on omitting C3b. We conclude that the ability to bind C5 is a property of C3b molecules whether surface bound or in free solution and that when C5 is bound in either fashion, it can be cleaved by a fluid phase C3/C5 convertase.

Animals↗
PubMed1996

Suppression of experimental crescentic-type anti-glomerular basement membrane (GBM) nephritis by FK506 (tacrolimus hydrate) in rats.

The effect of FK506 (tacrolims hydrate), an immunosuppressive agent produced by Streptomyces tsukubaensis, on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats was investigated. When rats were treated with FK506 from 1 or 20 days after the anti-GBM serum injection, FK506 inhibited the increase in urinary protein excretion. Histological observation demonstrated that FK506 suppressed glomerular alterations. In the FK506-treated rats, antibody production and rat-IgG and C3 deposits on the GBM were significantly less than those in the nephritic control group. FK506 treatment suppressed the accumulation of ED-1-positive cells, CD4-positive cells, CD8-positive cells, interleukin-2 (IL-2)-receptor-positive cells, leukocyte-function-associated antigen-1 (LFA-1)-positive cells and intercellular adhesion molecule-1 (ICAM-1)-expression in nephritic glomeruli. However, in the in vitro study, FK506 failed to inhibit the up-regulated ICAM-1 expression on endothelial cells in response to tumor necrosis factor (TNF)-alpha. On the other hand, IL-2 production from the spleen cells isolated from nephritic rats treated with FK506 was lower than that in the nephritic control rats. These results suggest that FK506 is effective against crescentic-type anti-GBM nephritis and that the antinephritic mechanisms of FK506 is due to the inhibition of intraglomerular accumulation and activation of leukocytes through the suppression of ICAM-1 expression and IL-2 production.

Animals↗
PubMedDate not supplied

[The activation of the complement system in various connective tissue diseases].

A knowledge of the complement system in patients with collagen diseases is of interest as it may serve to indicate the existence of activity or non-activity in these diseases. We have studied the existence or non-existence of the activity of the complement system through evaluation of the levels of C3, as well as the implicated mechanism of the classical or alternate pathways through the measure of C'4 and C'3 proactivator components. Quantitation of complement components was obtained by electroimmunodiffusion, employing specific antiserum. From the results obtained, we observed that the complement activity in patients with SLE, the classic pathway was affected more (7 patients of the 24 studied), than the alternate pathway (3 patients). However, in those patients affected by sclerodermia, there seems to be an equal incidence of the activation of complement through both pathways (2 patients with activation through each way). Also of interest is the existence of a patient with SLE and another affected by sclerodermia in which a selective reduction of C'3 was observed. This observation suggests the possible existence of a selective destruction, perhaps mediated through a factor type such as the nephritic factor. However, there may exist other patients of whom we have already commented on, with a parallel reduction in the three components which suggests a change in the synthesis or in the simultaneous activation in both of the pathways. When realizing the comparative studies of the state in which the immunoglobulins (IgG, IgA and IgM) and complement components are to be found, the conclusion is that there is no significative correlation between the two. This is particularly interesting as it assumes the necessity of knowing the state of the complement and not only of the immunoglobulin, in order to know the state of activity in which the process is.

Complement C3↗
PubMed1978

[Recurrence of intramembraneous glomerulonephritis in 2 consecutive kidney transplantations].

A case of dense intramembranous deposit disease, partial lipodystrophy, hypocomplementemia, and nephritic factor-like activity in the serum is presented. Recurrence of underlying renal disease was noted in two consecutive renal allografts. The first transplant was lost 7 months after implantation, chronic renal rejection being an additional cause of graft failure. A favourable clinical course, however, was observed after the second renal transplantation. 22 months after surgery, the patient was fully rehabilitated and transplant function only slightly reduced despite electron microscopic evidence of typical dense intramembranous deposit lesions. Low C3-serum complement and normal C4-serum complement levels were constant findings throughout observation time. The case supports the assumption that patients with dense intramembranous deposit disease should not be excluded from renal transplantation As shown in the literature, maintenance of satisfactory graft function is usually obtained for a long period of time despite recurrence of original disease.

Adult↗
PubMed1993

Immunohistochemical localization of C3d fragment of complement and S-protein (vitronectin) in normal and diseased human kidneys: association with the C5b-9 complex and vitronectin receptor.

The localization of C3d, a fragment produced by C3 activation and S-protein (vitronectin), a regulatory factor of C5b-9, was studied immunohistochemically in normal human kidney and renal biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that C3d was present along the glomerular basement membrane (GBM), tubular basement membrane (TBM) and arterioles, and that S-protein was present in the GBM, mesangium, TBM, and arterioles. Immunoelectron microscopy of isolated basement membranes showed that C3d was localized exclusively on the epithelial side of the GBM, and that S-protein was present along both the epithelial and endothelial sides. In nephritic tissues, glomerular staining of C3d, C5b-9, and S-protein was increased when compared with that in normal tissues. S-protein, frequently co-localized with C3d and C5b-9 neoantigen, was intensely positive in the immune deposits of glomerular capillaries and the mesangial area, overlapping the background staining of GBM and mesangial matrix. S-protein and its receptor were occasionally co-localized in the glomeruli. These findings indicate that C3d and S-protein are normally present in the glomeruli. Co-staining of C3d, C5b-9 neoantigen, and S-protein within the immune deposits of nephritic kidneys suggests in situ binding of S-protein to locally-formed C5b-9 complex, or merely co-distribution of S-protein with the complex, rather than trapping of large molecular SC5b-9 complex from the circulation.

Complement C3d↗
PubMed1993

Analysis of clinical and laboratory profile in Indian childhood systemic lupus erythematosus and its comparison with SLE in adults.

Data on the clinical and laboratory profiles of 83 children with SLE have been analysed and compared with data on 187 adults with the disease. The clinical features of childhood SLE are similar to those seen in adults, although clinical and laboratory parameters reflect propensity to a more severe form of the disease in the juvenile age group. However, in comparison to descriptions of childhood lupus from developed countries, in India the female-to-male ratio in this age group parallels that in adults. Renal involvement is noted to be more common, whereas gastro-intestinal and haematological abnormalities are less common. Interestingly, leucopenia, lymphopenia and nephritic type of renal involvement are commonly seen in boys with SLE, but these features are non-existent in men.

Adolescent↗
PubMed1995

Complement system promotes transfer of immune complex across glomerular filtration barrier.

BACKGROUND: The solubilizing effect of complement (C) on immune complexes (IC) in the fluid phase is well known, however effects on tissue-deposited IC have not been analyzed in detail. We studied the influence of C depletion on the movement of IC across the glomerular basement membrane in a rat model of passive in situ IC nephritis. EXPERIMENTAL DESIGN: The left kidneys of intact rats, rats given cobra venom factor (C-depleted) or rats given anti-polymorphonuclear granulocyte antiserum (PMN-depleted) were perfused with cationized ferritin (electron-dense tracer antigen), followed by intravenous injection of rabbit anti-ferritin antibody 15 minutes later. The glomerular distribution of rabbit IgG (antibody) and rat C3 was visualized by immunogold staining. RESULTS: In intact, nephritic rats (non C-depleted), the distribution of antigen, antibody, and C3 (IC) was mainly subendothelial 2 and 6 hours after antibody injection, at 24 hours about 75% and by 48 hours virtually all 3 IC components were localized on the subepithelial side of the glomerular basement membrane in all glomeruli. In C-depleted rats, the distribution of IC was as in intact rats, up to 6 hours. At 24 hours, two patterns of IC distribution within individual glomeruli could be distinguished. About 2/3 of the capillary wall area revealed a distribution similar to the C-intact animals; however in 1/3 of the capillary wall area, IC was still predominantly subendothelial at 24 hours. By 48 hours, some accumulation in the lamina densa was noted. At day 7, some IC was still subendothelial, in limited areas, even though serum C3 level had returned to 60% of normal. On the other hand, the distribution of IC in polymorphonuclear leukocyte-depleted, C-intact rats, showed no difference to that in control nephritic rats. Proteinuria was significantly decreased in both C-depleted rats and polymorphonuclear leukocyte-depleted rats. Thus, enhanced glomerular permeability itself does not guarantee complete, rapid IC movement. CONCLUSIONS: The C system promotes effective transfer of IC across the glomerular basement membrane, probably due to the solubilizing effect of C on IC lattices.

Animals↗
PubMed1991

Complement and monocytes are essential for provoking glomerular injury in passive Heymann nephritis in rats. Terminal complement components are not the sole mediators of proteinuria.

Complement but not polymorphonuclear granulocytes (PMN) causes glomerular injury in passive Heymann nephritis in rats. We have now identified monocytes as another important mediator in this model. Passive Heymann nephritis was induced in Wistar rats by intravenous injection of sheep anti-rat Fx1A antiserum. Four groups (all receiving anti-rat Fx1A antiserum) were studied: (a) rats given normal sheep globulin (nephritic controls), (b) rats given sheep anti-rat PMN globulin (PMN-depleted), (c) rats given sheep anti-rat monocyte globulin (monocyte-depleted), (d) rats injected with cobra venom factor (complement-depleted). In vitro specificity controls for anti-cell antisera were made by cytotoxicity tests and inhibition of phagocytosis. In vivo specificity controls were performed in heterologous Masugi nephritis (PMN-dependent) and accelerated Masugi nephritis (monocyte-dependent). Complement and monocyte depletion significantly delayed the onset of proteinuria (p less than 0.001 versus nephritic controls on day 5), PMN depletion had no significant effect. Monocyte infiltration was seen in control nephritic rats, but monocyte depletion prevented this influx. In the monocyte-depleted group, no differences in glomerular deposition of C3, C9, and C5b-9 were seen in comparison to the nephritic control rats. Serum C3 levels were comparable in groups a, b, and c, the complement system was biologically active in the monocyte depleted-group (c), and the amount of anti-Fx1A antibody bound was the same in all groups. This shows that, besides complement, monocytes are required for induction of renal damage in passive Heymann nephritis. The concept of a sole role for complement in glomerular immune injury involving subepithelial immune deposits should be reconsidered.

Animals↗