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L A Van Es

Publications and source records attributed to L A Van Es.

At least 19 recordsLinked to original sources
PubMed1999

The terminal sequence of complement plays an essential role in antibody-mediated renal cell apoptosis.

Mesangial cell (MC) injury is a characteristic feature in the early phase of Thy.1 nephritis. The present study investigates the contribution of complement to MC apoptosis in this experimental model of kidney disease in rats. Thy.1 nephritis was induced by injection of mouse anti-Thy.1 monoclonal antibody (ER4G). To assess the contribution of the terminal sequence of complement on apoptosis, the studies were performed in complement-sufficient PVG/c (PVG/c+) rats and in rats deficient in complement C6 (PVG/c-). Apoptosis was monitored by assessment of the number of condensed nuclei in kidney sections stained with periodic acid-Schiff (PAS) and by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method and expressed as number of apoptotic cells per 50 glomerular cross sections. In the PAS method, 1 h after intravenous injection of ER4G, PVG/c+ rats exhibited 160.9 +/- 49.5 apoptotic cells, whereas PVG/c- rats had only 3.2 +/- 1.4 apoptotic cells. Control rats exhibited 0.9 +/- 0.6 apoptotic cells. These findings were confirmed with the TUNEL method. In PVG/c- rats, a maximum number of 8.8 +/- 3.1 TUNEL-positive (TUNEL+) cells was found at 6 h followed by a decline thereafter. In PVG/c+ rats, apoptosis was associated with deposition of C6 and C5b-9. Restoration of the complement system of PVG/c- rats with purified human C6 resulted in an increase of apoptosis at 1 h after injection of ER4G from minimal numbers to 239.9 +/- 52.4 TUNEL+ cells. These studies appear to indicate for the first time that the terminal sequence of complement is involved in induction of apoptosis.

Analysis of Variance↗
PubMed1999

Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2.

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Adult↗
PubMed1998

Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection.

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted organs. In the present study, the possible role of interleukin-17 (IL-17), a recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted to the activation of nonhematopoietic cells. In vitro, IL-17 induced primary human proximal tubular epithelial cells, a type of cell regulating local interstitial inflammatory responses, to secrete higher levels of IL-6, IL-8, and monocyte chemoattractant protein-1, but not of the chemokine RANTES. The effect was specific for IL-17, because it was completely abrogated by a neutralizing anti-IL-17 antibody and was demonstrated to be dose- and time-dependent. In addition, IL-17 increased the production of complement component C3 by human proximal tubular epithelial cells, but not of other complement components. Immunofluorescence showed expression of IL-17 in kidney biopsies from patients suffering from graft rejection (8 of 8 positive), whereas pretransplant biopsies and normal kidneys were negative (0 of 6). Analysis of whole kidney isolates confirmed the presence of IL-17 mRNA by reverse transcription-PCR. IL-17 expression could also be found in in vitro cultured and activated graft-infiltrating T cells. These results represent the first demonstration of IL-17 protein expression in pathologic conditions and suggest that IL-17 might be important in the regulation of local inflammatory responses.

Base Sequence↗
PubMed1997

Antigen-antibody complexes enhance the production of complement component C3 by human mesangial cells.

Deposition of immune complexes (ICX), with or without complement, occurs in various forms of glomerulonephritis. It has been reported that upregulation of complement C3 mRNA expression is found in kidneys of patients with ICX glomerulonephritis. In vitro studies have indicated that mesangial cells (MC) synthesize C3. Furthermore, MC express Fc gammaRIII receptors. This study investigates whether ICX alter C3 and factor H production by MC. MC were cultured in medium alone or in medium with insoluble heat-aggregated rat IgG (AIgG) or with insoluble ICX. Basal production of C3 and factor H was 10 +/- 1 ng/10(6) and 605 +/- 15 ng/10(6) cells, respectively. The presence of 400 microg/ml AIgG or ICX resulted in upregulation of C3 production to 999 +/- 15 ng/10(6) and 510 +/- 1 ng/10(6) cells, respectively, whereas no significant change in factor H production was observed. The upregulation of C3 was inhibitable by cycloheximide, suggesting that de novo protein synthesis was required. By reverse transcription PCR and Northern blot analysis, it was demonstrated that C3 and interleukin-6 mRNA expression was upregulated in MC after incubation with AIgG. No detectable change in factor H mRNA expression was seen. In conclusion, it is shown that incubation of MC with AIgG or ICX not only results in upregulated production of inflammatory mediators such as cytokines, but also leads to an upregulation of C3 synthesis. Therefore, it is hypothesized that ICX deposited within the mesangium may enhance the local production of C3 via interaction with Fc receptors on MC.

Actins↗
PubMed1996

Interleukin-1 alpha enhances the biosynthesis of complement C3 and factor B by human kidney proximal tubular epithelial cells in vitro.

Local production in tubular cells of complement has been shown to occur in several kidney diseases by in situ hybridization, but the regulation at the local site during an inflammation is still unknown. In the present study, we demonstrate that human proximal tubular epithelial cells (PTEC) are able to produce complement components C3 and Factor B under non-stimulated conditions in vitro. The basal production of both was increased by 0.5 ng/ml interleukin-1 alpha (IL-1 alpha) for C3: from 95.5 +/- 4.0 ng/10(6) cells to 416.5 +/- 4.9 ng/10(6), and for Factor B: from 271 +/- 7.0 ng/10(6) cells to 457.5 +/- 7.0 ng/10(6) cells. In contrast cytokines such as TNF-alpha, IFN-gamma, IL-10 and IL-15 had no detectable effect. The upregulation by IL-1 alpha was dose- and time-dependent. The response to IL-1 alpha was shown to be mediated via the IL-1 receptor, as the addition of recombinant interleukin-1 receptor antagonist inhibited the IL-1 alpha induced complement production by more than 80%. IL-1 alpha enhanced mRNA expression of both C3 and Factor B as demonstrated by RT-PCR and dot-blot analysis. This indicated that IL-1 alpha upregulated the expression of the C3 and Factor B at the transcriptional level. We hypothesize that in vivo the production of C3 and Factor B at the local site during an inflammatory response in the kidney may be regulated by IL-1 alpha produced by inflammatory cells.

Cell Line↗
PubMed1996

Transforming growth factor-beta 1 (TGF-beta 1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes.

IgA is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis. The clearance of IgA is dependent on the function of at least three types of receptors. One of these receptors recognizes the Fc portion of the IgA molecule, Fc alpha R, which has been cloned recently. Fc alpha R, also designated CD89, is found on a number of cells, including human glomerular mesangial cells, and monocytes. In this study we analysed the effect of TGF-beta 1, a cytokine with strong immunosuppressive function, on the expression of CD89 on freshly isolated monocytes. We found that TGF-beta 1 down-regulates CD89 expression on human peripheral blood monocytes in a dose-dependent fashion. Optimal down-regulation occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-beta 1 is linear in time, with a mean down-regulation of 34 +/- 13% after 24 h. Also at the mRNA level, CD89 expression was down-regulated by TGF-beta 1, suggesting regulation of CD89 at the transcriptional level. Monocytes pre-treated with TGF-beta 1 displayed a reduced response to IgA, as measured by IL-6 production by monocytes, in contrast to monocytes pre-treated with medium alone. These results suggest an important role for TGF-beta 1 in the regulation of CD89. This down-regulation may have direct consequences for the handling of IgA by human monocytes.

Antigens, CD↗
PubMed1996

Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro.

A number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10.8 +/- 1.5 ng IL-8 per 1 x 10(5) cells in 72 h. Gel filtration chromatography of PTEC supernatant indicated that the size of IL-8 of PTEC is 15.1 and 8.1 kD, and is chemotactically active for polymorphonuclear neutrophils (PMN). Addition of 0.5 ng/ml rIL-1 alpha or 1000 U/ml recombinant tumour necrosis factor-alpha (rTNF-alpha) to the culture media of PTEC induced an up-regulation of IL-8 production up to 6.3-fold and 3.0-fold, respectively. The up-regulation by IL-1 alpha and TNF-alpha was dose- and time-dependent. In contrast, 500 U/ml recombinant interferon-gamma (rIFN-gamma) down-regulated the production of IL-8 3.4-fold. Northern blot analysis showed that IL-1 alpha and TNF-alpha increased the expression of IL-8 mRNA, whereas IFN-gamma reduced IL-8 mRNA expression. Taken together, these experiments indicate that human PTEC are a potential source of IL-8 in the kidney, and that IL-8 produced in the proximal tubule can be induced by various proinflammatory cytokines.

Cells, Cultured↗
PubMed1992

CD59 expressed by human endothelial cells functions as a protective molecule against complement-mediated lysis.

CD59 is a 18-20-kDa membrane glycoprotein that inhibits formation of the membrane attack complex of complement (C) on homologous cells. In the present study we analyzed the expression and function of CD59 on human endothelial cells. Immunohistochemical analysis of renal cortex demonstrated a predominant expression of CD59 on peritubular capillary endothelial cells and glomerular endothelial cells. Flow cytometry analysis showed that human umbilical vein endothelial cells (HUVEC) expressed CD59 and the fluorescence intensity was approximately four times that of peripheral blood lymphocytes. CD59 is detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single 20-kDa molecule in 2% deoxycholate extracts of HUVEC. CD59 was released from the surface of HUVEC by phosphatidylinositol-specific phospholipase C, demonstrating that it is attached to the cell membrane by means of a glycolipid anchor. The functional activity of CD59 expressed on HUVEC was studied. Blocking of CD59 antigen with F(ab')2 fragments of polyclonal anti-CD59 enhanced markedly the susceptibility of HUVEC to C-mediated lysis. This effect was dependent on the amount of blocking antibodies added. Northern blot analysis revealed the presence of three species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for CD59, with sizes of about 800, 1400 and 2000 bp. These findings suggest that CD59 may be important in protection of endothelial cells against C-mediated damage at local sites of inflammation, thereby maintaining the vascular integrity in vivo.

Antigens, CD↗
PubMed1992

In vivo activation of complement by IgA in a rat model.

In this study we investigated the capacity of rat IgA to activate complement (C) in vivo in a rat model. Rat monomeric (m-), dimeric (d-) and polymeric (p-) IgA MoAbs were injected intravenously and assessed for deposition of C3 and C4 on IgA. By ELISA it was shown that both d- and p-IgA bound C3 whereas no binding of C3 by m-IgA was observed. Polymeric IgA was more efficient in binding of C3 as compared with d-IgA. However, in haemolytic assays no consistent decrease of plasma complement levels was observed except for dimeric IgA which induced a marginal consumption of AP50. When rats were pre-treated with cobra venom factor (CVF) to deplete C3, no C3 deposition was found on m-, d- or p-IgA. Neither m- nor d- or p-IgA was able to bind C4 in vivo. In agreement with the results described above, large sized polymeric IgA was shown to be taken up by Kupffer cells (KC) together with C3. No C3 was detected when rats were depleted of C using CVF. Taken together, the experimental data suggest that d- and p-IgA are able to activate C via the alternative pathway in vivo.

Animals↗
PubMed1991

Complement enhances the clearance of large-sized soluble IgA aggregates in rats.

In the present study the involvement of the complement system (C) in the clearance of soluble IgA aggregates in the rat was studied. Monoclonal monomeric IgA (mIgA) antibody (which does not activate C) or aggregated polymeric IgA (aIgA; which activates C) were administered intravenously to phosphate-buffered saline-treated and complement-depleted [Cobra venom factor (CVF)-treated] rats and assessed for clearance from the circulation. In control rats, mIgA was cleared in a biphasic fashion with a first half-life (T1/2) of 29.5 +/- 14.2 min and a second T1/2 of 230 +/- 176 min. No differences were observed in clearance of mIgA in CVF-treated rats as compared to PBS-treated rats. In PBS-treated rats, aIgA with a size between 20 S and 150 S disappeared very rapidly from the circulation with a first T1/2 of 1.1 +/- 0.4 min and a second T1/2 of 23.2 +/- 11.3 min. In CVF-treated rats the clearance of aIgA was significantly delayed as compared to that in control rats, namely with a first T1/2 of 7.3 +/- 2.6 min and a second T1/2 of 64.2 +/- 19.4 min. Immunohistochemical studies of the liver (which is the main site of clearance of aIgA) revealed that Kupffer cells (KC) are mainly responsible for the uptake of aIgA. Furthermore, in PBS-treated rats aIgA deposition was accompanied by C3 deposition in the KC. In CVF-treated rats, the percentage of KC containing aIgA was significantly lower during the first 16 min after aIgA administration as compared to PBS treated rats. In addition no detectable C3 was found in KC of CVF-treated rats. These results indicate that KC play an important role in the clearance of large molecular weight IgA in rats and that C facilitates the clearance of these complexes from the circulation.

Animals↗
PubMed1990

Evaluation of the efficiency of two IgA immune complex assays.

Two IgA immune complex assays, namely the anti-IgA inhibition of binding assay (a-IgA-InhBA) and the IgA polyethylene glycol assay (IgA-PEG assay) were evaluated using IgA aggregates (AIgA) of well defined sizes. AIgA was prepared by heat treatment. After ultracentrifugation the size of AIgA was found to be in a range between 7 S and 64 S. Five AIgA pools (greater than 64 S, 44-64 S, 24-43 S, 20-24 S and 9-19 S) and a pool of monomeric IgA were prepared to test the efficiency of the two assays. The IgA-PEG assay exclusively detected very large sized AIgA (greater than 64 S), whereas the a-IgA-InhBA detected also AIgA of intermediate size (9-19 S). The sensitivity of the latter assay was found to be size dependent. After ultracentrifugation of serum samples from patients with IgA nephropathy, IgA of large and intermediate macromolecular size was detected. It is concluded that the a-IgA-InhBA is useful for the detection of circulating IgA-containing immune complexes in IgA nephropathy.

Antigen-Antibody Complex↗
PubMed1990

Specificity and cross-reactive idiotypes of anti-gp330 autoantibodies in active Heymann nephritis.

The aim of this study was to characterize the epitope specificity and the idiotype(s) of gp330-specific autoantibodies in active Heymann nephritis (HN). To study this, two monoclonal autoantibodies (mAb), 3D9B and 5B8C, derived from Lewis rats with HN, were generated. These antibodies bound to different epitopes on the autoantigen gp330, as shown by in vitro studies. In order to characterize the idiotype(s) of the mAb, rabbit anti-idiotypic antisera were prepared. It was shown that the rabbit antisera directed against the 3D9B as well as the 5B8C idiotype were able to inhibit the binding of nephritic eluate to gp330. This indicated that the idiotypes recognized on 3D9B and 5B8C were relevant to the spectrum of idiotypes involved in HN. In order to investigate the nature of the two idiotypes of these mAb, cross-absorption and binding studies were performed. The rabbit antisera raised against one of the two idiotypes bound in a direct binding ELISA to both idiotypes. Since the observed cross-reactivity of the antisera suggested that the idiotypes of 3D9B and 5B8C were at least partly cross-reactive, homologous polyclonal and monoclonal anti-idiotypic antibodies were prepared by immunizing rats with 3D9B or 5B8C. The results from the binding and inhibition experiments strongly suggest that the idiotypes of 3D9B and 5B8C contain cross-reactive or public idiotopes.

Animals↗
PubMed1989

Clearance kinetics and tissue distribution of aggregated human serum IgA in rats.

In the present study the clearance kinetics and tissue distribution of human polyclonal heat-aggregated serum IgA (AIgA) of different sizes in rats was studied after intravenous administration of 125I-AIgA. The 125I-AIgA of different sizes disappeared from the circulation in a biphasic manner with an initial rapid half-life (T1/2) and a second slower T1/2. The first T1/2 was related to the size of the 125I-AIgA: high molecular weight (MW) 125I-AIgA was cleared much faster than 125I-AIgA with a low MW. Relatively more degradation products were observed in blood when high MW 125I-AIgA were injected as compared to low MW 125I-AIgA. The AIgA were mainly taken up by the liver. Eight minutes after injection of high MW 125I-AIgA, 90% of the injected dose was found in the liver, whereas less than 2% was detected in the spleen. Very little activity was detectable in other organs, such as lungs, heart and kidneys. In the present study 1-3% of the injected 125I-AIgA were found in the bile. Analysis of this material revealed that low MW 125I-AIgA were transported more efficiently to the bile than high MW 125I-AIgA. To obtain more insight into the receptors involved in the clearance of 125I-AIgA, rats were pretreated with ovalbumin or asialofetuin. The clearance of 125I-AIgA of different sizes was inhibited when rats were pretreated with asialofetuin. Pretreatment with ovalbumin had no effect on the clearance rates of 125I-AIgA. These results suggest a role for carbohydrate receptors, which recognize glycoprotein-containing galactose terminal residues on Kupffer cells, in the clearance of 125I-AIgA.

Animals↗
PubMed1989

Complement-mediated enhancement of IgA-induced H2O2 release by human polymorphonuclear leucocytes.

In a previous study we have demonstrated that heat-killed Staphylococcus aureus opsonized with either purified human serum IgA or secretory IgA (sIgA) can induce a respiratory burst (measured as H2O2 release) in human polymorphonuclear leucocytes (PMN; Gorter et al., 1987). In the present study we have investigated whether opsonization of IgA-coated staphylococci with complement has an additional effect on the H2O2 release of PMN. It was demonstrated that staphylococci coated with IgA (or sIgA) and subsequently opsonized with complement induced at least a two-fold increase in the specific H2O2 release compared with bacteria coated with IgA (or sIgA) alone (P less than 0.05 and P less than 0.02, respectively). The co-operative effect of IgA and complement was also observed in the presence of 10 mM ethyleneglycoltetraacetic acid containing 5 mM MgCl2 (MgEGTA), suggesting that activation of the alternative pathway of complement is sufficient to exert this effect. Using D-deficient serum as a source of complement we could demonstrate that activation of the alternative pathway is essential for the co-operative effect of complement and IgA. The increase in specific H2O2 release caused by complement was found to be dependent on the amount of IgA initially used to opsonize the bacteria. Finally the co-operative effect of IgA and complement was not restricted to one IgA subclass, because an additional opsonization of S. aureus coated with sIgA1 or sIgA2 with complement resulted in both cases in a statistically significant enhanced specific H2O2 release by PMN (P less than 0.05).

Complement C3↗
PubMed1989

Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.

To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.

Adult↗
PubMed1988

The complement subcomponent C1q mediates binding of immune complexes and aggregates to endothelial cells in vitro.

The present studies were initiated to investigate whether soluble immune complexes, upon interaction with complement, can bind to endothelial cells. Human umbilical vein endothelial cells (HUVE) were incubated with purified human 125I-labeled C1q at 4 degrees C in RPMI-0.5% bovine serum albumin and assayed for binding. Optimal binding of 125I-labeled C1q to HUVE was reached within 2 h, and saturation of binding was found at concentrations of 5 micrograms/well input. The binding of 125I-labeled C1q was inhibitable with unlabeled C1q and by the collagenous region of pepsin-cleaved C1q. No inhibition was observed with the globular heads of C1q, suggesting that C1q binds to HUVE via the collagenous region of C1q. When HUVE were first reacted with various concentrations of C1q, washed and subsequently incubated with 125I-labeled aggregated human IgM (AIgM), binding of 125I-labeled AIgM to HUVE occurred depending on the dose of C1q. Only those aggregates of IgM which react with C1q in a solid-phase C1q binding assay were able to bind to HUVE presensitized with C1q. In addition it was shown that C1q mediated binding of aggregated IgG to HUVE. Furthermore, immune complexes (IC), that were prepared with bovine thyroglobulin (BTg) and rabbit anti-BTg, bound to C1q-preincubated HUVE. These studies suggest that localization of IC on endothelium can be enhanced following interaction of the IC with complement.

Antigen-Antibody Complex↗
PubMed1988

Activation of rat complement by soluble and insoluble rat IgA immune complexes.

The ability of rat monoclonal IgA, specific for 2,4-dinitrophenyl (DNA), to activate the complement (C) system of the rat was investigated using aggregated IgA or IgA immune complexes (IC). IgA was coated onto a solid phase, and tested for its capacity to bind C3 upon incubation at 37 degrees C in normal rat serum (NRS) in the presence of Mg-EGTA. Binding of C3 was observed dependent on the dose of dimeric (d-), polymeric (p-) and secretory IgA tested. In contrast, little C3 fixation was observed in this system with monomeric (m-) rat IgA or with mouse m- and d-IgA (MOPC315). Soluble and insoluble rat IgA IC were prepared using dinitrophenylated rat serum albumin (DNP8RSA) as antigen (Ag), and assessed for C activation. It was shown that insoluble IC (immune precipitates; IP) containing m-, d- or pIgA of rat origin activate the alternative pathway of rat C, as demonstrated by their capacity to induce C consumption in NRS in the presence of Mg-EGTA. When p- and m-IgA IP were compared for their capacity to activate C, it was found that p-IgA activated C four times as efficiently as m-IgA IP (at 2 mg/ml). Soluble rat IgA IC were prepared in an excess of DNP8RSA, fractionated by gel filtration on Sepharose 6B, and analyzed for C activation and antibody (Ab)/Ag ratio. In contrast to m-IgA IP, soluble m-IgA did not activate C. On the other hand soluble d-IgA IC activated C dependent on their concentration and size: at a concentration of 0.1 mg/ml high-molecular weight d-IgA IC with a high Ab/Ag ratio were four times as efficient as low-molecular weight IC with a low Ab/Ag ratio, and twice as efficient as IP prepared at equivalence. To demonstrate the induction by IgA of the assembly of the terminal membrane attack complex, trinitrophenyl (TNP)-conjugated rat red blood cells (TNP-RRBC) coated with d- or p-IgA were shown to be lysed in NRS in the presence of Mg-EGTA. No lysis of m-IgA-coated TNP-RRBC was observed. The results in this study demonstrate that both soluble and insoluble rat IgA IC activate the alternative pathway of homologous rat C. Alternative pathway activation by soluble rate IgA IC is dependent on the size of the IC. The degree of polymerization of the IgA Ab itself also influences C activation.

Animals↗