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Biomedical subjects

M R Daha

Publications and source records attributed to M R Daha.

At least 199 records · Page 11Linked to original sources
PubMed1994

Binding of surfactant protein A to C1q receptors mediates phagocytosis of Staphylococcus aureus by monocytes.

During both steady-state conditions and inflammatory reactions in the lower airways, monocytes migrate to the alveoli where they come into contact with surfactant. Surfactant is composed of phospholipids, neutral lipids, and specific proteins, and its main function is to reduce surface tension in the alveoli. The most abundant glycoprotein surfactant protein A (SP-A) affects the structure, function, and metabolism of pulmonary surfactant. The aim of the present study was to determine whether SP-A plays a role in the antibacterial activities of human monocytes and whether this is mediated by a receptor for SP-A on these cells. The results showed that SP-A binds to both Staphylococcus aureus and monocytes and mediates the phagocytosis of the bacteria by these cells. SP-A does not stimulate the intracellular killing of bacteria by monocytes, and SP-A-opsonized S. aureus do not induce the production of reactive oxygen intermediates. SP-A binds to the C1q receptor (C1qR) on monocytes, since its binding was inhibited by C1q and the SP-A-enhanced association of S. aureus with these cells was completely abolished when monocytes were adherent to surfaces coated with C1q or anti-C1qR monoclonal antibody. Furthermore, the binding of SP-A to monocytes results in an increased intracellular concentration of adenosine 3',5'-cyclic monophosphate. Together, these results demonstrate that C1qR mediates the phagocytosis of SP-A-opsonized S. aureus by monocytes.

Calcium↗
PubMed1994

Antiendothelial cell antibodies in systemic lupus erythematosus: enhanced antibody binding to interleukin-1-stimulated endothelium.

IgG antiendothelial antibodies (IgG AEA), as measured by enzyme-linked immunosorbent assay, could be detected in serum samples of 38 out of 41 patients with systemic lupus erythematosus. Incubation of endothelial cells (EC) with interleukin-1 alpha (IL-1 alpha), in contrast to incubation with interferon gamma or tumor necrosis factor alpha, resulted in an enhanced IgG AEA binding. Immunoblotting revealed reactivity of AEA against a variety of EC antigens. The upregulation of IgG-AEA-binding reactivity to IL-1 alpha-stimulated EC was due to binding to antigens that were already expressed by unstimulated EC. The IgG-binding reactivity to both IL-1 alpha-stimulated and unstimulated EC was significantly higher in the serum of patients with joint or skin abnormalities as compared with patients without these manifestations. These data suggest that upregulated binding of IgG to EC induced by IL-1 alpha may play a role in immune vascular damage.

Adult↗
PubMed1994

Recognition of a tissue-specific polymorphism by graft infiltrating T-cell clones isolated from a renal allograft with acute rejection.

Acute interstitial rejection is an important clinical problem after cadaver kidney transplantation. Recently we have reported that six of 17 graft-infiltrating cell (GIC) lines isolated from kidneys undergoing such rejection episodes recognize graft-derived proximal tubular cells but not lymphoid cells from the same donor. In this study we characterized the specificity of one such GIC line in more detail. From this T-cell line, 18 cytotoxic T-cell (CTL) clones were isolated. Four of these were also cytotoxic against donor lymphoid cells. Nine tissue-specific clones were selected for further analysis. They all contained CD8+ and TCR alpha/beta+ cells and cytotoxicity by these cells was class I restricted. Only proximal tubular epithelial cells (PTEC) expressing HLA-A31 (an antigen present in the donor but absent in the recipient) were recognized by all clones. There were, however, three clones that did not lyse all HLA-A31+ PTEC lines, demonstrating recognition of an HLA-A31 tissue-associated polymorphism. Thus during rejection episodes after renal transplantation GIC may recognize various tissue-derived peptides bound to a mismatched HLA molecule on the cell surface of renal parenchymal cells. These GIC are likely to contribute to the observed destruction of tubuli during episodes of acute rejection after kidney transplantation.

Adult↗
PubMed1993

Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts.

C plays a critical role in the hyperacute rejection (HAR) of discordant xenografts (Xg), but the relative contribution of early vs late C components is unknown. In this study, genetic differences in C6 activity were correlated with HAR of guinea pig cardiac Xg by the rat. Seven rat strains were tested for C activity. Six strains (PVG.R1 (R1), PVG.1A (1A), DA, W/F, F344, LEW) had readily detectable C activity in the total and alternative pathways. Some PVG rats also had adequate C activity [PVG (C+)] but others [PVG (C-)] had a profound C6 deficiency. All rats with adequate C activity (n = 35) rejected cardiac Xg between 15 and 80 min. PVG (C+) (n = 6) rats also rejected cardiac Xg hyperacutely (26 +/- 12 min), whereas PVG (C-) (n = 16) rats, which had high preformed IgM natural antibody titers, rejected cardiac Xg in 1 to 2 days (2678 +/- 542 min). Transfer of serum from R1 rats to PVG (C-) recipients with vigorously beating Xg caused HAR of cardiac Xg within 116 +/- 75 min. Transfer of fresh PVG (C-) serum or heat-inactivated R1 serum did not induce HAR. HAR was characterized by intravascular platelet aggregation and interstitial hemorrhage, whereas Xg transplanted to PVG (C-) recipients had patent vessels at 30 min but were heavily infiltrated by granulocytes and monocytes at 2 days. These findings indicate that a deficiency in C6 prevents HAR but allows an accelerated acute rejection that may be mediated by the generation of vasoactive and chemotactic C3a and C5a.

Animals↗
PubMed1993

C1Q, a subunit of the first component of complement, enhances the binding of aggregated IgG to rat renal mesangial cells.

Previous reports have shown the presence of C1Q-R on monocytes, macrophages, polymorphonuclear cells, fibroblasts, platelets, lymphocytes, and endothelial cells. The present study demonstrates a functional C1Q-R on rat renal mesangial cells (MC). Incubation of MC with increasing concentrations of [125I]C1Q resulted in a dose-dependent binding of [125I]C1Q to MC; the binding of [125I]C1Q was inhibitable by excess unlabeled C1Q or C1Q stalks whereas BSA and C1Q globular heads had no effect. Scatchard analysis of the data revealed the presence of 6.2 x 10(7) binding sites/cell with an affinity of 4.9 x 10(6) M-1 for C1Q. Immunoprecipitation of 125I-labeled MC membrane proteins with C1Q or mAb directed against human C1Q-R revealed a single 66- to 68-kDa band under reducing conditions. We have shown previously that soluble stable aggregates of IgG bind to rat MC in a dose-dependent fashion. In addition the presence of a receptor for IgG has been described on rat MC. In order to find out whether there is a cooperative effect between C1Q and AlgG in binding of [125I]AlgG to MC, we incubated [125I]AlgG in the presence of increasing concentrations of C1Q, and showed a 5- to 15-fold enhancement of binding of [125I]AlgG to MC. Neither heat-inactivated C1Q nor C1Q stalks were able to enhance the binding of [125I]AlgG to MC. Enhanced binding by C1Q was only observed when aggregated IgG was used; the binding of monomeric IgG to MC was not affected by C1Q. These studies indicate that there is a cooperative effect between Fc gamma R and C1Q-R on MC in the recognition of immune complexes.

Animals↗
PubMed1993

[Complement deficiencies and meningococcal disease in The Netherlands].

OBJECTIVE: To determine the prevalence of complement system deficiencies in patients who have survived a Neisseria meningitidis infection. DESIGN: Retrospective. SETTING: Reference laboratory for bacterial meningitis of the University of Amsterdam and the National Institute of Public Health and Environmental Protection. METHOD: Out of the files of the laboratory 187 patients who had experienced a meningococcal infection in the Netherlands between 1959-1990 were selected in two groups according to the infecting bacterial strain: 97 patients with a serogroup X, Y, Z, W135, 29E, or non-groupable strains and 90 patients with an infection due to serogroup A or C. The patients were asked for their cooperation by their family doctor and one of us visited the patients at home to take blood samples. The complement activity was studied with a haemolysis in gel test and with an assay of haemolytic activity in free solution. RESULTS: Complement deficiency was present in 18% of the 187 patients who had experienced a meningococcal infection. The highest prevalence was found in patients older than 10 years who had developed infections due to serogroups X, Y, W135, or non-groupable strains (45%). Of the patients with a serogroup A or C infection, 3% had an complement deficiency. Of the complement deficiencies, 42% concerned a component of the alternative pathway, 12% a deficiency of C3, and 46% a component of the terminal route. The most commonly found deficiencies were properdin deficiency (39%) and C8 deficiency (18%). 30% of the complement deficient patients reported other family members having experienced meningitis. Recurrent meningitis was only observed in patients with terminal route deficiencies. CONCLUSION: We recommend that patients with a meningococcal infection due to serogroups X, Y, W135 or non-groupable strains should be screened for complement deficiency.

Adolescent↗
PubMed1993

The value of indirect immunofluorescence and solid phase techniques for ANCA detection. A report on the first phase of an international cooperative study on the standardization of ANCA assays. EEC/BCR Group for ANCA Assay Standardization.

This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Isolation of a protein complex from purulent sputum consisting of proteinase-3 and alpha 1-antitrypsin reactive with anti neutrophil cytoplasmic antibodies.

The detection of ANCA (anti-neutrophil cytoplasmic antibodies) is of importance in the diagnosis of Wegener's granulomatosis (WG) and solid-phase assays for the detection of c-ANCA have been set up by various groups, using purified proteinase-3 (PR-3) in an ELISA or RIA. For the isolation of PR-3 large numbers of PMNs are needed. We therefore examined the possibility of isolating PR-3 from the purulent sputum of patients with chronic bronchitis or cystic fibrosis, since large numbers of PMNs and their degranulation products are present in such material. By a three-step chromatographic procedure (4-phenylbutylamine affinity chromatography, Biorex 70 cation exchange chromatography and monoclonal antibody anti-PR-3 affinity chromatography) we isolated a 53 kDa protein that was recognized on immunoblot by MoAbs directed against PR-3 and alpha 1-antitrypsin (alpha 1AT). We show that the 53 kDa protein is a complex of PR-3 and alpha 1AT. This complex is reactive with a selected set of c-ANCA positive sera from patients with Wegener's granulomatosis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

A novel ELISA assay for the detection of C3 nephritic factor.

We have developed an ELISA procedure for the detection of C3 nephritic factor (C3NeF), in which wells are coated with a fixed concentration of 2 micrograms C3b per well, and subsequently reacted with B and D. The presence of increasing concentrations of NiCl2 showed a NiCl2 concentration-dependent generation of C3bBb and very little solid-phase bound C3bBb was generated with MgCl2. The formation of solid-phase C3bBb in the presence of an optimal concentration of 1 mM NiCl2, was time-dependent and plateau values were reached after 30 min at 37 degrees C. IgG purified from the serum of a patient with membranoproliferative glomerulonephritis (MPGN) type II containing C3NeF stabilizing activity was bound to the C3bBb generated on microwells in a dose-dependent manner whereas normal IgG exhibited only minor reactivity. C3NeF activity was measured using the ELISA method in patients with MPGN type II (n = 15) and other diseases (n = 17) and in normal controls (n = 15). Most of the patients with MPGN type II exhibited positive C3NeF at various levels, while two of the disease controls showed only slight reactivities. C3NeF titers measured by this new ELISA procedure correlated well with previously described hemolytic assays (r = 0.617, p < 0.01).

Complement C3 Nephritic Factor↗
PubMed1993

Complement enhances the elimination of soluble aggregates of IgG by rat liver endothelial cells in vivo.

In the present study, we have investigated the role of complement (C) and possible C receptors present on rat liver endothelial cells (EC) in the clearance and tissue distribution of soluble aggregates of IgG (AIgG). To study the effect of elimination of AIgG by EC in vivo, Kupffer cell (KC)-depleted rats were used, with or without an intact C system (These rats will be referred to throughout this report as EC-rats.) In EC-rats with an intact C system, clearance of AIgG (2000-3000 kDa, 20-27 IgG molecules/aggregate) occurred in a biphasic manner with a first T 1/2 (T1) of 9.4 +/- 2.3 min and a second T 1/2 (T2) of 44.7 +/- 16.0 min. In EC-rats without an intact C system [cobra venom factor (COVF)-treated group], clearance of AIgG was significantly delayed with a T1 of 25.3 +/- 9.9 min (p < 0.005) and a T2 of 124.5 +/- 18.4 min (p < 0.001). There were less degradation products of AIgG in the circulation in EC-rats treated with COVF as compared to EC-rats with an intact C system. Eight minutes after injection, 27.5 +/- 11.6% of the injected AIgG was found in the livers of EC-rats while 15.1 +/- 3.2% was found in the livers of the COVF-treated group. Double immunofluorescence studies indicated that AIgG in the liver was associated with EC in the rats with an intact C system. Clear deposits of C3 and lesser amounts of C1q accompanied the deposition of AIgG. In COVF-treated EC-rats, AIgG together with C1q was also associated with EC but no detectable C3 was seen. These data suggest clearance of AIgG via Fc and C receptors present on EC in vivo.

Animals↗
PubMed1993

Role of liver endothelial and Kupffer cells in clearance of human C1q in rats.

In the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) C1q in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu C1q were measured. In untreated rats, the clearance of hu C1q occurred in a monophasic manner with a half-life of 66 +/- 26.7 min. The clearance of hu C1q in KC-depleted rats was delayed significantly (p < 0.001) and occurred with a half-life of 217 +/- 78.8 min. Fifteen min after injection, 11 +/- 3.5% of hu C1q was found in the liver of untreated rats and 8 +/- 1.4% was found in the liver of KC-depleted rats. The percentage non-trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of C1q, reached a level of 11.6 +/- 5.6% at 240 min in untreated rats compared with 4.6 +/- 5.8% in KC-depleted rats. Double immunofluorescence staining 5 min after administration of C1q in untreated rats, revealed that C1q was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu C1q, there was an uptake of C1q in the hepatocytes. In KC-depleted rats, 5 min after administration of hu C1q, C1q was bound to the EC. Fifteen minutes after injection, C1q was also found in the hepatocytes. Electron microscopical studies revealed that C1q binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu C1q in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade C1q, and that EC may play a role in the handling of C1q and C1q bound to immune complexes.

Animals↗
PubMed1993

Schistosoma mansoni circulating anodic antigen but not circulating cathodic antigen interacts with complement component C1q.

Adult schistosome parasites, living in the blood vessels of their mammalian hosts, protect themselves against immune damage in a variety of ways. In addition to the tegument, the intestinal epithelium of the blood-feeding worms is permanently exposed to both the innate and the acquired immune system. In this study, we investigated whether the Schistosoma gut-associated antigens CAA and CCA (circulating anodic antigen and circulating cathodic antigen, respectively), which are excreted in relatively large quantities into the host's circulation, might play a role in evading complement attack. Of several complement components tested, only purified C1q showed significant binding to CAA, a negatively charged highly glycosylated glycoprotein. CCA, also highly glycosylated, but neutral or slightly positively charged, did not bind to C1q. CAA bound only to the collagen-like stalks of C1q and not to the globular heads. No detectable interaction of CAA with precursor human C1 was found and CAA did not induce activation of C1 in whole human serum as assessed by consumption of hemolytic C4 activity. Also CAA could not induce activation of precursor C1 in vitro. These results suggest that CAA behaves like a receptor for C1q, and might be involved in protecting the vulnerable schistosome gut against complement-mediated attack.

Animals↗
PubMed1993

Cleavage and inactivation of human C1 inhibitor by the human leukocyte proteinase, proteinase 3.

Incubation of highly purified human C1 inhibitor with equally pure human leukocyte proteinase 3, resulted in a dose- and time-dependent inactivation of C1 inhibitor hemolytic activity. Furthermore, this inactivation was accompanied by proteinase 3-dependent cleavage of the C1 inhibitor into an 83,000 molecular weight fragment. The formation of the 83,000 molecular weight fragment followed a time course which was similar to that observed for the inactivation of hemolytic activity. Within 120 minutes more than 90% of the hemolytic activity was lost. This inactivation of C1 inhibitor appeared to be selective as purified human C1q was not degraded in a similar time period. Moreover, when 100 micrograms IgG, isolated from each of 21 Wegener's granulomatosis patients with cytoplasmic anti-nuclear antibodies immunofluorescent titers to proteinase 3 greater then 1:64, was incubated with 3 milliunits of proteinase 3, little to no cleavage of C1 inhibitor was observed. In contrast, 100 micrograms of IgG isolated from 14 normal donors was ineffective in affording protection to C1 inhibitor upon incubation with proteinase 3. Our results suggest that neutrophil infiltration and activation could lead to local complement consumption at the tissue sites.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Detection of intracellular interferon-gamma by light microscopy using an immunoperoxidase technique: correlation with the corresponding mRNA and protein product.

Identifying individual cytokine-producing cells may help to acquire insight into immunological processes. This study was designed to adapt a technique for the detection of individual cytokine-producing cells from an immunofluorescence to an immunoperoxidase staining procedure. The production of interferon-gamma (IFN-gamma) by anti-CD3-activated cloned human T cells was used as a model system. After the conditions for the staining procedure were optimized, the immunoperoxidase technique was slightly more sensitive than the immunofluorescence technique. The intracellular staining for IFN-gamma was preceded or paralleled by IFN-gamma mRNA production and followed by accumulation of IFN-gamma in the supernatant. It is concluded that intracellular IFN-gamma can easily be detected using an immunoperoxidase procedure. This procedure is highly sensitive and allows quantification of the production of multiple cytokines by counting the percentage of positively staining cells.

Cytokines↗
PubMed1993

Activated synovial T cell clones from a patient with rheumatoid arthritis induce proliferation of autologous peripheral blood-derived T cells.

In order to investigate cellular interactions involved in the development of human autoimmune disease, a synovial fluid-derived T cell clone reactive with mycobacterial antigens, termed k38, was employed as a stimulus for autologous peripheral blood mononuclear cells (PBMC). Stimulator cells were used either activated with immobilized OKT3 mAb or in a resting state. Activated k38 cells triggered PBMC to proliferate. A T cell line prepared by coculturing autologous PBMC with irradiated activated k38 cells proliferated upon stimulation with activated k38 cells in the presence of PBMC as a source of accessory cells, as did T cell clones that were subsequently isolated from this line. Blocking studies revealed that proliferation of the anti-k38 line and anti-k38 clones in response to stimulation with clone k38 could be inhibited by monoclonal antibodies against a variety of cellular determinants including HLA class I and LFA-1 beta. It was demonstrated that the antigen reactivity of clone k38 was modulated by the presence of anti-k38 clones. These data provide a model for understanding the cellular interactions that may take place in vivo in the evolution of the chronic synovial inflammatory process.

Antibodies, Monoclonal↗
PubMed1993

The relationship between serum titers of autoantibodies to C1q and age in the general population and in patients with systemic lupus erythematosus.

The aim of the present study was to assess the relationship between age and titers of autoantibodies to C1q (C1qAb) in individuals randomly selected out of the general population and in systemic lupus erythematosus (SLE) patients. Serum samples of 659 randomly selected individuals and 169 SLE patients were divided into 6 age groups from 20 to 79 years. IgG and IgA C1qAb titers were measured by ELISA. The highest titers of IgG and IgA C1qAb in sera of randomly selected individuals were found in the oldest age groups. In serum of SLE patients the highest titers of IgG C1qAb were found in the youngest age groups, whereas IgA C1qAb titers did not change with aging. It is concluded that the distribution pattern of IgG and IgA C1qAb titers in serum of individuals randomly selected out of the general population is similar to that of other autoantibodies. The increased titers of IgG C1qAb in serum of young patients with SLE suggest a role of these antibodies in the pathogenesis of the disease.

Adolescent↗
PubMed1993

Effects of inoculation with attenuated autologous T cells in patients with rheumatoid arthritis.

Injection of attenuated autoimmune T cells, T cell vaccination, has been used successfully in the prevention and treatment of experimental animal autoimmune disease. In order to determine whether such a procedure might be applied in rheumatoid arthritis (RA), a phase I study was conducted in thirteen RA patients with a mean disease duration of 12.8 years. All patients received a subcutaneous injection of attenuated autologous T lymphocytes from a CD4 positive clone (n = 4) or line (n = 9) isolated from synovial tissue (n = 3) or synovial fluid (n = 10). No toxic side effects were observed. On the average the patients showed a slight decrease in disease activity which was most marked at 8 weeks after the injection. Specific immune reactivity against the injected T cells was not detected, with the possible exception of one patient who was vaccinated with a clone selected in vitro with antigen and whose disease had begun one year earlier. In this patient a clear decrease in disease activity occurred, which was associated with a decrease in mitogen-induced proliferation of her peripheral blood mononuclear cells and in titres of serum rheumatoid factors. The results of this study show that inoculation of RA patients with autologous T cells is technically feasible and non-toxic, and may be associated with clinical and immunological effects. The data suggest that the potential of T cell vaccination should be further explored in diseases with defined antigen reactivity.

Adult↗