Immune-complex-induced transglutaminase activation: its role in the Fc-receptor-mediated transmembrane effect on peritoneal macrophages.
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Biomedical subjects
Publications and source records attributed to J Gergely.
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The effect of anti-beta 2 m-specific autoantibodies was investigated on the FcRs of human PBMCs. Anti-beta 2 m autoantibodies inhibited the FcRs of the lymphocyte subpopulation detectable by rosetting with EA(hu). On the contrary, when EA(ox) indicator system was used, in the majority of the cases an enhancement of EA rosette formation was detected. Using separated lymphocyte subpopulations we found that the binding of anti-beta 2 m autoantibodies increased the number of FcR+ non-B-cells and inhibited that of B-lymphocytes.
In a previous investigation, inhibition of complement-dependent rosette formation by alpha 1-antitrypsin (alpha 1-AT) was observed, and it was demonstrated that alpha 1-AT interacts through its carbohydrate portion with C3 and its fragments. In the present study, the effect of alpha 1-AT on the complement-receptor-mediated phagocytosis by human peripheral blood monocytes was examined. Purified alpha 1-AT inhibited in a dose-dependent manner phagocytosis of C3-carrying yeast particles. Inhibition was selective, concerned only C3-receptor-mediated phagocytosis, neither Fc-receptor-mediated phagocytosis nor uptake of untreated yeast particles was blocked by alpha 1-AT. It was demonstrated that alpha 1-AT towards C3 and fragments of C3 was not mediated by its antiprotease effect, but by its carbohydrate moiety. This finding suggests that alpha 1-AT may have an impact on various immune functions involving complement receptors.
Authors performed by using various tests serial examinations of the circulating immune complex (IC) concentration in healthy persons, untreated rats, as well as in patients with multiple myeloma or leukemia, and in immunocytoma bearing rats. A characteristic fluctuation of the IC values has been observed in the untreated rats and the healthy persons. The discrepant IC values obtained in the identical sample with the different tests suggest the heterogeneity of IC components. As compared to healthy individuals a significantly higher fluctuation of IC values has been found characteristic in immunocytoma. Authors analyzed the composition of IC and discussed the possible importance of the tumor specific antigens and the natural antibodies reacting with them.
The capacity was studied of bovine serum albumin (BSA) rabbit anti-BSA and ovalbumin (OA) rabbit anti-OA immune complexes of different composition to inhibit the Fc receptor-dependent adherence and phagocytosis of sensitized sheep red blood cells by human monocytes. Parallel experiments were performed on the ability of the immune but complement-reacted complexes to inhibit the C3 receptor-dependent phagocytosis of C3-coated yeast particles. The extent of inhibition of both the Fc and C3 receptor-dependent phagocytosis was proportional to the antibody avidity of the complex used. Immune complexes made at equivalence and at moderate antibody excess markedly inhibited both types of phagocytosis, whereas those made at moderate antigen excess had only a weak inhibitory effect. These findings can be explained by the correlation between the Fc receptor-binding and complement-activating capacities of immune complexes of different composition. An alternative explanation, however, is also discussed.
Antibodies against the dinitroaminophenyl (DNAP) haptenic group were raised in outbred CFY rats using HSA or LPS as carrier. Antibodies isolated by immunoadsorbent techniques were resolved into fractions representing distinct isotypes, and the resulting fractions were tested for avidity. Subclass IgG2a was found to contain antibodies of an avidity index lower than those of other IgG subclasses or IgM. IgG2a was the only isotype detected when DNAP-LPS was used for immunization. Complexes containing defined isotypes were compared for their capacity to activate homologous complement. IgGl type antibody-containing complexes displayed a low complement activating capacity compared with those containing IgG2b, IgG2c or IgG2a. The latter subclass when complexed with antigen can thus induce complement-dependent processes in spite of a low avidity. Insoluble complexes of IgG antibodies were rapidly solubilized in rat serum (CRA phenomenon), except those containing predominantly IgG2c.
Comparison of proton magnetic resonance spectra of a tryptic and a thrombin fragment of troponin-C with that of the native protein has identified the domain of the molecule influenced by Ca2+ binding to the lower affinity regions I and II of troponin-C. The binding of Ca2+ to these sites results in a subtle alteration of the tertiary fold of the N-terminal half of troponin-C involving weakened contacts between several hydrophobic groups. The role and kinetics of the movements within the troponin-C molecule associated with binding at the regulatory sites are discussed.
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The rotational motion of crossbridges, formed when myosin heads bind to actin, is an essential element of most molecular models of muscle contraction. To obtain direct information about this molecular motion, we have performed saturation transfer EPR experiments in which spin labels were selectively and rigidly attached to myosin heads in purified myosin and in glycerinated myofibrils. In synthetic myosin filaments, in the absence of actin, the spectra indicated rapid rotational motion of heads characterized by an effective correlation time of 10 microseconds. By contrast, little or no submillisecond rotational motion was observed when isolated myosin heads (subfragment-1) were attached to glass beads or to F-actin, indicating that the bond between the myosin head and actin is quite rigid on this time scale. A similar immobilization of heads was observed in spin-labeled myofibrils in rigor. Therefore, we conclude that virtually all of the myosin heads in a rigor myofibril are immobilized, apparently owing to attachment of heads to actin. Addition of ATP to myofibrils, either in the presence or absence of 0.1 mM Ca2+, produced spectra similar to those observed for myosin filaments in the absence of actin, indicating rapid submillisecond rotational motion. These results indicate that either (a) most of the myosin heads are detached at any instant in relaxed or activated myofibrils or (b) attached heads bearing the products of ATP hydrolysis rotate as rapidly as detached heads.
Laser Raman spectroscopy has been used detect structural changes in troponin C induced by Ca2+ binding. Addition of Ca2+ - Mg2+ sites produces perturbations in the amide III region of the spectrum indicative of increased alpha-helical content, and in regions of the spectrum corresponding to carboxylate, thiol, and phenol side chains. However, Ca2+ binding to the low affinity Ca2+ - specific sites is not detected by laser Raman spectral changes.
Association of small unilamellar vesicles (SUV) can be effectively targeted to normal human peripheral mononuclear blood cells (PMBC). - Lymphocytes of chronic lymphoid leukaemic (CLL) patients show a low rate of liposome association, which cannot be improved by targeting with anti-lymphocyte globulin (ALG). Presence of serum evoked an enhanced association of liposomes to PMBC.
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Macrophage-cytophilic antibody activity of various immunoglobulin classes and subclasses was tested in two different rosetting systems. Cytophilic antibody activity of IgM, IgG2a and IgG1 was verified in the SRBC system, while IgM, IgG2a and IgG2c were found to be active in the trypanosome system. Sensitivity to cytochalasin B treatment of SRBC rosette formation was dependent on the class of antibody and decreased in the following order: IgM > IgG1 > IgG2a. Trypanosome rosette formation was prevented by the same drug regardless the type of antibody. Vinblastin caused an enhancement of rosette formation in the SRBC system in low concentration, except when the antibody belonged to subclass IgG1. The enhancing effect was less pronounced in the trypanosome system.
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