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PubMed2001

Factors affecting humic-nickel complex mediated reduction of trichloroethene in homogeneous aqueous solution.

The kinetics of trichloroethene (TCE) reductive dechlorination mediated by humic-Ni complexes in homogeneous aqueous solution using titanium(III) citrate as the bulk reductant was examined under various environmental conditions (e.g., pH and ionic compositions). Using Ca2+, Zn2+, and Hg2+ ions to vary Aldrich humic acid (HA)-Ni complex concentrations, pseudo-first-order rate constants for TCE reduction were observed to be proportional to HA-Ni levels (as calculated by speciation modeling), confirming HA-Ni complexes as the probable active mediator species. TCE reduction by HA-Ni was observed to be strongly pH dependent and could be due to both the variations of HA-Ni concentration and Eh with pH. Evidence is presented which suggests that quinone moieties may not be crucial for the humic-Ni mediated reduction of TCE. A variety of natural soil and aqueous humic material and Ni systems were examined, and some showed reactivity toward TCE. Humic-metal complexes may be important electron-transfer mediators in natural systems.

Benzoquinones↗
PubMed2006

Hereditary nephritis mimicking immune complex-mediated glomerulonephritis.

The defining ultrastructural features of hereditary nephritis are "basket weave" lamellation or thinning of glomerular basement membranes. Electron-dense deposits are not seen and immunofluorescence (IF) is generally negative. In this study, we report 5 cases of hereditary nephritis in which substantial amounts of glomerular electron-dense deposits were identified on electron microscopy, with corresponding positive IF staining in 4 cases, suggesting immune complex-mediated glomerulonephritis. However, no case had histological evidence of glomerular endocapillary or extracapillary proliferation or leukocyte infiltration typical of active glomerulonephritis. Four cases were diagnosed at outside institutions simply as forms of glomerulonephritis without considering the possibility of hereditary nephritis and were sent for consultation in contemplation of possible immunosuppressive therapy. All patients had negative serologies and no known underlying infectious or autoimmune disease; 4 patients had family history of hematuria or renal disease. The glomerular electron-dense deposits were predominantly mesangial (4 cases) and intramembranous (4 cases), as well as subepithelial (2 cases) or subendothelial (1 case). Corresponding IF positivity for immune reactants was identified in 4 cases, and IgG was the predominant immunoglobulin deposited. A characteristic feature was the tendency for deposits to form between the complex layers of glomerular basement membrane material, favoring a process of nonspecific entrapment of immune reactants within the thickened, lamellated basement membrane. In all cases, a diagnosis of hereditary nephritis was confirmed by demonstration of the characteristic loss of immunoreactivity for the alpha5 subunit of collagen IV (4 cases) or Goodpasture's antigen (1 case) in renal or epidermal basement membranes. These cases expand the spectrum of unusual pathological findings in hereditary nephritis and emphasize the potential for hereditary nephritis to mimic immune complex glomerulonephritis.

Adolescent↗
PubMed1986

Ultrastructural localization of extracellular immunoglobulins in immune-complex-mediated glomerulonephritis. Immunoelectron microscopy of Epon-embedded human renal biopsies using the immunogold staining procedure.

The ultrastructural localization of immunoglobulins (Igs) in immunologically mediated glomerulonephritis was achieved in ultrathin sections of glutaraldehyde-fixed, post-osmicated, Epon-embedded human renal needle biopsies using the indirect immunogold staining procedure. Extracellular Igs were identified in electron-dense deposits in subendothelial, intramembranous, subepithelial and mesangial locations in different cases of immune-complex-mediated glomerulonephritis. The excellent preservation of the ultrastructural morphology of the tissue sections made it possible to precisely correlate the presence and distribution of the antigens with those of the electron-dense deposits, which are the ultrastructural hallmarks of these diseases. Our post-embedding staining procedure which allows extracellular Igs to the accurately localized should be a very useful tool for immunomorphological investigations of glomerulonephritis.

Glomerulonephritis↗
PubMed2003

A peptide derived from the parasite receptor, complement C2 receptor inhibitor trispanning, suppresses immune complex-mediated inflammation in mice.

Complement C2 receptor inhibitor trispanning (CRIT) is a Schistosoma protein that binds the human complement protein, C2. We recently showed that peptides based on the ligand binding region of CRIT inhibit the classical pathway (CP) of complement activation in human serum, using hemolytic assays and so speculated that on the parasite surface CRIT has the function of evading human complement. We now show that in vitro the C2-binding 11-aa C terminus of the first extracellular domain of CRIT, a 1.3-kDa peptide termed CRIT-H17, inhibits CP activation in a species-specific manner, inhibiting mouse and rat complement but not that from guinea pig. Hitherto, the ability of CRIT to regulate complement in vivo has not been assessed. In this study we show that by inhibiting the CP, CRIT-H17 is able to reduce immune complex-mediated inflammation (dermal reversed passive Arthus reaction) in BALB/c mice. Upon intradermal injection of CRIT-H17, and similarly with recombinant soluble complement receptor type 1, there was a 41% reduction in edema and hemorrhage, a 72% reduction in neutrophil influx, and a reduced C3 deposition. Furthermore, when H17 was administered i.v. at a 1 mg/kg dose, inflammation was reduced by 31%. We propose that CRIT-H17 is a potential therapeutic agent against CP complement-mediated inflammatory tissue destruction.

Animals↗
PubMed1993

Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.

Animals↗
PubMed1998

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with immune complex-mediated glomerulonephritis in chronic active EB virus infection.

Renal involvement is rare in chronic active Epstein-Barr (EB) virus infection. We report a case of a 7-year-old girl with recurrent EB virus infection. She had fever, lymphadenopathy, hepatosplenomegaly, and persistently high titres of IgG to EB virus capsid antigen (VCA) and IgG to EB early antigen with low titres of IgM to VCA. She showed mild haematuria and proteinuria, but had no symptoms of renal failure. Renal biopsy revealed immune complex-mediated glomerulonephritis, which may have been due to a persistently high titre of antibody against EB virus. In addition, a peculiar form of tubulointerstitial nephritis was found. The morphology was characterized by a papillary infolding of the tubular epithelial cell layer into the tubular lumen. The interstitium was surrounded by the infolded epithelium and contained a large number of B-cell dominant lymphocytes. EBV-encoded RNA 1 (EBER-1) gene was detected in the nuclei of some tubuloepithelial cells by in situ hybridization and may have been associated with the pathogenesis of tubulointerstitial nephritis.

Biopsy↗
PubMed1997

The adenovirus E3-10.4K/14.5K complex mediates loss of cell surface Fas (CD95) and resistance to Fas-induced apoptosis.

Cytotoxic T cells use Fas (CD95), a member of the tumor necrosis factor (TNF) receptor superfamily, to eliminate virus-infected cells by activation of the apoptotic pathway for cell death. The adenovirus E3 region encodes several proteins that modify immune defenses, including TNF-dependent cell death, which may allow this virus to establish a persistent infection. Here we show that, as an early event during infection, the adenovirus E3-10.4K/14.5K complex selectively induces loss of Fas surface expression and blocks Fas-induced apoptosis of virus-infected cells. Loss of surface Fas occurs within the first 4 h postinfection and is not due to decreased production of Fas protein. The decrease in surface Fas is distinct from the 10.4K/14.5K-mediated loss of the epidermal growth factor receptor on the same cells, because intracellular stores of Fas are not affected. Further, 10.4K/14.5K, which was previously shown to protect against TNF cytolysis, does not induce a loss of TNF receptor, indicating that this complex mediates more than one function to block host defense mechanisms. These results suggest yet another mechanism by which adenovirus modulates host cytotoxic responses that may contribute to persistent infection by human adenoviruses.

Adenovirus E3 Proteins↗
PubMedDate not supplied

Collagen induced arthritis: an experimental model for rheumatoid arthritis with involvement of both DTH and immune complex mediated mechanisms.

The type II collagen induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and is also a useful model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA when induced with autologous type II collagen, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases autoantibodies to type II collagen and rheumatoid factors are produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells. We suggest here that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA could provide a tool for studies of immunospecific reactions leading to arthritis.

Animals↗
PubMed2003

A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans.

Negative regulation of receptor tyrosine kinase (RTK)/RAS signaling pathways is important for normal development and the prevention of disease in humans. We have used a genetic screen in C. elegans to identify genes that antagonize the activity of activated LET-23, a member of the EGFR family of RTKs. We identified two loss-of-function mutations in dpy-22, previously cloned as sop-1, that promote the ability of activated LET-23 to induce ectopic vulval fates. DPY-22 is a glutamine-rich protein that is most similar to human TRAP230, a component of a transcriptional mediator complex. DPY-22 has previously been shown to regulate WNT responses through inhibition of the beta-catenin-like protein BAR-1. We provide evidence that DPY-22 also inhibits RAS-dependent vulval fate specification independently of BAR-1, and probably regulates the activities of multiple transcription factors during development. Furthermore, we demonstrate that although inhibition of BAR-1-dependent gene expression has been shown to require the C-terminal glutamine-rich region, this region is dispensable for inhibition of RAS-dependent cell differentiation. Thus, the glutamine-rich region contributes to specificity of this class of mediator protein.

Animals↗
PubMed2000

Mouse toll-like receptor 4.MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol.

Taxol, an antitumor agent derived from a plant, mimics the action of lipopolysaccharide (LPS) in mice but not in humans. Although Taxol is structurally unrelated to LPS, Taxol and LPS are presumed to share a receptor or signaling molecule. The LPS-mimetic activity of Taxol is not observed in LPS-hyporesponsive C3H/HeJ mice, which possess a point mutation in Toll-like receptor 4 (TLR4); therefore, TLR4 appears to be involved in both Taxol and LPS signaling. In addition, TLR4 was recently shown to physically associate with MD-2, a molecule that confers LPS responsiveness on TLR4. To determine whether TLR4.MD-2 complex mediates a Taxol-induced signal, we constructed transformants of the mouse pro-B cell line, Ba/F3, expressing mouse TLR4 alone, both mouse TLR4 and mouse MD-2, and both mouse MD-2 and mouse TLR4 lacking the cytoplasmic portion, and then examined whether Taxol induced NFkappaB activation in these transfectants. Noticeable NFkappaB activation by Taxol was detected in Ba/F3 expressing mouse TLR4 and mouse MD-2 but not in the other transfectants. Coexpression of human TLR4 and human MD-2 did not confer Taxol responsiveness on Ba/F3 cells, suggesting that the TLR4. MD-2 complex is responsible for the species specificity with respect to Taxol responsiveness. Furthermore, Taxol-induced NFkappaB activation via TLR4.MD-2 was blocked by an LPS antagonist that blocks LPS-induced NFkappaB activation via TLR4.MD-2. These results demonstrated that coexpression of mouse TLR4 and mouse MD-2 is required for Taxol responsiveness and that the TLR4.MD-2 complex is the shared molecule in Taxol and LPS signal transduction in mice.

Animals↗
PubMed1993

Immune complex-mediated glomerulopathy in Barbus graellsi infected with Myxobolus spp.

Membranous glomerulonephritis caused in Barbus graellsi by myxosporidian infections have been studied by electron microscopy and immunoelectron microscopy techniques. This study indicates that Myxosporidian infection produces a chronic severe aggression. Spores reach the spleen, the kidney and the liver, where they are trapped and phagocyted by Melano Macrophage Centres. Consequently, the commencement of a immunological response to myxosporidian is evident. Our results show the presence of immunodeposits in the basement membrane of the glomeruli, suggesting that they might initiate glomerulonephritis. The lesion was markedly similar to immune complex-mediated glomerulonephritis disease in higher vertebrates.

Animals↗
PubMed1992

Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis.

Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury.

Amino Acid Sequence↗
PubMed1998

[Immune complex-mediated glomerulonephritis associated with infective endocarditis with aortic valve vegetation].

A 61-year-old male was referred to our hospital for rapidly progressive azotemia. He was also found to have huge vegetation at the aortic valve causing regurgitation. Biochemical examinations revealed the presence of an immunocomplex associated with decreased circulating complements. In biopsy samples from the kidney, we found the presence of fibrillar crescents, proliferation of mesangial cells, increase in extracellular matrix proteins, atrophy of tubules, infiltration of mononuclear cells in the interstitial regions, high density deposits in the mesangial area and mesangial interposition. Since the patient strongly rejected operative treatment by valvular replacement, we continued non-invasive treatment such as hemodialysis and treatment with penicillin G. This transiently improved the condition of the patient, including biochemical data and cardiac function, but there was no reduction in the size of vegetation at the aortic valve and the bacteria responsible for infective endocarditis were not identified. About three months after admission, overt signs of congestive heart failure emerged and the patients was subjected to intensive care with a respirator and hemodynamic monitoring. Although the cardiac function was improved, concomitant severe pneumonia occurred and the patient died of septic shock. Thus, we report a rare case in whom immune complex-mediated glomerulonephritis was associated with infective endocarditis with aortic valve vegetation.

Antigen-Antibody Complex↗
PubMed1985

Necrotic changes of the spinal cord with immune-complex-mediated disseminated vasculitis in a case of atypical allergic encephalomyelitis.

A 42-year-old woman demonstrated recurrent, progressive neurological symptoms of peripheral and central nervous system damage of undefined infectious origin. Laboratory investigations showed abnormalities in the CSF and serum, suggesting subacute viral infection. Neuropathological examination revealed complete, widespread necrosis in the cervical and thoracic segments of the spinal cord with mononuclear and microglial infiltrations. There was pronounced thickening and fibrinoid necrosis of the vessel walls with mononuclear cuffs along the spinal cord. Dispersed, similar but less intensive inflammatory changes were present in the medulla oblongata, midbrain and basal ganglia. Surprisingly, there was diffuse demyelination with only slight glial and inflammatory reactions throughout the white matter of both hemispheres. The finding of coarse- and fine-grained deposits of IgG and C3 component of complement in the vessel walls of the spinal cord and vasa nervorum of cervical roots and peripheral spinal nerves, together with positive heterologous complement binding and the results of glycine-HC1 buffer elution, suggested immune-complex-mediated disseminated vasculomyelinopathy of the CNS and PNS. Consequent local ischemic changes and hypersensitivity phenomena led to frank necrosis of the cervical spinal cord and to extreme white matter demyelination in the brain. The case was diagnosed as allergic encephalomyelitis in which diffuse demyelination occurred coincidentally with spinal cord necrosis.

Adult↗
PubMed2000

Assembly of scaffold-mediated complexes containing Cdc42p, the exchange factor Cdc24p, and the effector Cla4p required for cell cycle-regulated phosphorylation of Cdc24p.

In budding yeast cells, the cytoskeletal polarization and depolarization events that shape the bud are triggered at specific times during the cell cycle by the cyclin-dependent kinase Cdc28p. Polarity establishment also requires the small GTPase Cdc42p and its exchange factor, Cdc24p, but the mechanism whereby Cdc28p induces Cdc42p-dependent polarization is unknown. Here we show that Cdc24p becomes phosphorylated in a cell cycle-dependent manner, triggered by Cdc28p. However, the role of Cdc28p is indirect, and the phosphorylation appears to be catalyzed by the p21-activated kinase family member Cla4p and also depends on Cdc42p and the scaffold protein Bem1p. Expression of GTP-Cdc42p, the product of Cdc24p-mediated GDP/GTP exchange, stimulated Cdc24p phosphorylation independent of cell cycle cues, raising the possibility that the phosphorylation is part of a feedback regulatory pathway. Bem1p binds directly to Cdc24p, to Cla4p, and to GTP-bound Cdc42p and can mediate complex formation between these proteins in vitro. We suggest that Bem1p acts to concentrate polarity establishment proteins at a discrete site, facilitating polarization and promoting Cdc24p phosphorylation at specific times during the cell cycle.

Adaptor Proteins, Signal Transducing↗
PubMed1984

Immune complex mediated lung haemorrhage and nephritis--successful treatment with plasma exchange, haemodialysis and immunosuppressive drug therapy.

A 16-year-old boy developed an immune complex illness associated with lung haemorrhage, proliferative nephritis with crescents and renal failure. Treatment with plasma exchange, haemodialysis and immunosuppressive drugs resulted in a rapid reduction in levels of immune complexes and other mediators of inflammation and was associated with good recovery of renal and lung function. Subsequently, deterioration in renal function occurred whilst the patient was on treatment with prednisolone alone but this was reversed with a short course of plasma exchange and the addition of azathioprine. No further deterioration in renal or lung function has been observed during 18 months treatment with azathioprine and prednisolone. Immediate plasma exchange and immunosuppressive drug treatment have been recommended for Goodpasture's syndrome. Immune complex mediated lung haemorrhage and nephritis is the main clinical differential diagnosis. Our case suggests that the same treatment is effective for both conditions if given early, and that detailed renal and immunological investigations should not be allowed to delay this.

Adolescent↗
PubMedDate not supplied

Experimental otitis media with effusion: an immune-complex-mediated response.

The possibility that immune complexes cause otitis media with effusion (OME) has been previously proposed. In order to test this hypothesis we developed an animal model in which immune complexes were injected into the middle ears of chinchillas and the animals killed at various time intervals thereafter. Moderate inflammatory changes were seen in animals killed four hours postinjection, whereas intense inflammation was observed in those killed at 24 hours. Inflammatory changes observed included capillary dilatation with increased capillary permeability, migration of polymorphonuclear leukocytes into the sub-mucosa, hemorrhage, and damage to and actual disruption of the subepithelial basement membrane. These changes are consistent with a complement-mediated acute inflammatory reaction. Although no definite conclusion can be made concerning the etiologic role of immune complex in OME, our findings show that immune complexes can cause acute inflammatory changes in the middle ear of the experimental animal.

Animals↗
PubMed2003

[Study on corelation between InsP(3) generation and TCR/ CD3 complex-mediated [Ca(2+)]i responses in T cells from SLE patients].

AIM: To demonstrate whether function disorder of T cells from SLE patients was relative to abnormal biochemical pathways mediated by TCR/ CD3 complex and whether this abnormality was relative to the InsP(3) production. METHODS: Human T cells were isolated through Nylon-columns from heparinized peripheral blood from SLE patients and control individuals. Percentage of CD3(+) T cells was detected by flow cytometry. After cross-linking of anti-CD3 mAbs to sheep anti-mouse IgG and stimulating T cells, the changes of free calcium ion within T cells was observed successively for 10 minutes by an adhesion cytometry. Flow cytometry was used to detect the difference in positive rate between normal individual's and SLE patient's T cells. Level of InsP(3) was detected by a radioreceptor assay kit. RESULTS: (1)Flow cytometry analysis showed that CD3(+) T cells obtained through nylon column accounted for more than 90%.(2)The base line recordings of [Ca(2+)]i response from SLE patients were similar to that from normal control (P=0.105). Peak and plateau [Ca(2+)]i response in T cells of SLE patients were significantly higher than that in the control group (P<0.001). (3)The percentage of the CD3(+) T cells was similar in both individuals (P=0.665).(4)No differences in the anti-CD3 mAb-mediated InsP(3) generation were found between the two groups (P=0.537). CONCLUSION: TCR/ CD3-mediated [Ca(2+)]i responses in T cells from SLE patients is abnormal, and the abnormality has no relation to InsP(3) generation.

Animals↗