The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform

H. Valdimarsson - One of the best experts on this subject based on the ideXlab platform.

  • Opsonization and antibodies to capsular and cell wall polysaccharides of streptococcus pneumoniae
    The Journal of Infectious Diseases, 1994
    Co-Authors: Gestur Viðarsson, Steinn Jonsson, Ingileif Jonsdottir, H. Valdimarsson
    Abstract:

    Opsonin-dependent phagocytosis is believed to be the major defense mechanism against Streptococcus pneumoniae. In addition to type-specific antibodies to pneumococcal capsular polysaccharides (PPS), most persons also produce antibodies to cell wall polysaccharide (CWPS), which may be detected in antibody assays due to contamination of PPS antigens. Antibodies to CWPS and PPS from common serotypes were analyzed in relation to opsonic activity before and after vaccination of healthy adults. A highly significant relationship was generally found between Opsonization and pneumococcal antibody levels, and this correlation increased markedly by neutralization of CWPS antibodies. This applied in particular for IgG2, which showed no correlation without neutralization. Adsorption of PPS antibodies almost abolished the opsonic activity, whereas removal of CWPS antibodies had no effect. These findings indicate that Opsonization of pneumococci is almost exclusively mediated by PPS antibodies and emphasize the importance of neutralizing CWPS antibodies when immunity to this organism is evaluated.

  • IgG Subclass Response and Opsonization of Streptococcus pneumoniae after Vaccination of Healthy Adults
    The Journal of Infectious Diseases, 1990
    Co-Authors: E. Bardardottir, Steinn Jonsson, I. Jonsdottir, A. Sigfusson, H. Valdimarsson
    Abstract:

    Studies relating Opsonization and IgG antibodies to Streptococcus pneumoniae have yielded contradictory results. This study compared changes in Opsonization with IgG subclass response after vaccinating healthy subjects with a 23-valent pneumococcal vaccine. Total IgG and IgG subclass antibodies to pneumococcal polysaccharide types 8, 9, and 19 were measured by ELISA. Opsonic activity was assayed using 3H-labeled bacteria and polymorphonuclear leukocytes in different serum concentrations (5%-40%). A substantial postvaccination increase in total and subclass IgG antibody was observed in most subjects, although variations were seen. Postvaccination sera generally gave rise to enhanced Opsonization, and a correlation was found between increases in antibody levels and Opsonization. This correlation was closest for IgG1 and IgG4 and generally strongest at the lowest serum concentration, but weak or absent at the highest concentration. Thus, vaccination against S. pneumoniae stimulates a variable increase in specific opsonic activity in health persons that is best demonstrated when serum is a limiting factor in the opsonin assay.

Kenji M Cunnion - One of the best experts on this subject based on the ideXlab platform.

  • complement regulator c4bp binds to staphylococcus aureus surface proteins sdre and bbp inhibiting bacterial Opsonization and killing
    Results in Immunology, 2013
    Co-Authors: Pamela S Hair, Caitlin K Foley, Neel K Krishna, Julius O Nyalwidhe, Joan A Geoghegan, Timothy J Foster, Kenji M Cunnion
    Abstract:

    Staphylococcus aureus is a premier human pathogen and the most common cause of osteoarticular, wound, and implanted device infections. We recently demonstrated S. aureus efficiently binds the classical complement regulator C4b-binding protein (C4BP) inhibiting antibody-initiated complement-mediated Opsonization. Here we identify S. aureus surface protein SdrE as a C4BP-binding protein. Recombinant SdrE and recombinant bone sialoprotein-binding protein (Bbp), an allelic variant of SdrE, both efficiently bound to C4BP in heat-inactivated human serum. We previously described SdrE as binding alternative pathway regulator factor H. Recombinant SdrE and Bbp efficiently bound C4BP and factor H in serum without apparent interference. Gain of function studies utilizing Lactococcus lactis clones expressing SdrE or Bbp increased serum C4BP and factor H binding, compared with empty-vector control (WT) approximately 2-fold. Correspondingly, classical pathway-mediated C3-fragment Opsonization and bacterial killing by human neutrophils decreased by half for L. lactis clones expressing SdrE or Bbp compared with WT. In summary, we identify SdrE and allelic variant Bbp as S. aureus surface proteins that bind the complement regulator C4BP inhibiting classical pathway-mediated bacterial Opsonization and killing.

Dmitri Simberg - One of the best experts on this subject based on the ideXlab platform.

  • Immunoglobulin deposition on biomolecule corona determines complement Opsonization efficiency of preclinical and clinical nanoparticles.
    Nature Nanotechnology, 2019
    Co-Authors: Geoffrey Gifford, Halli Benasutti, Robert I Scheinman, Guankui Wang, Ernest Groman, Fangfang Chen, Laura Saba, Seyed Moein Moghimi, Dmitri Simberg
    Abstract:

    Deposition of complement factors (Opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that Opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 Opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 Opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and Opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 Opsonization, and may determine individual complement responses to nanomedicines.

  • in vitro and in vivo differences in murine third complement component c3 Opsonization and macrophage leukocyte responses to antibody functionalized iron oxide nanoworms
    Frontiers in Immunology, 2017
    Co-Authors: Guankui Wang, Seyed Moein Moghimi, James I Griffin, Swetha Inturi, Barbara Brenneman, Nirmal K Banda, Michael V Holers, Dmitri Simberg
    Abstract:

    Balancing surface functionalization and low immune recognition of nanomedicines is a major challenge. Opsonization with the third component of the complement protein (C3) plays a major role in immune cell recognition of nanomedicines. We used dextran coated superparamagnetic iron oxide nanoworms (SPIO nanoworms) to study the effect of surface functionalization on C3 Opsonization in mouse serum and subsequent macrophage/leukocyte recognition in vitro as well as on intravenous injection into mice. Previously we found that in mouse serum, SPIO nanoworms became opsonized with C3 via complement lectin pathway. Crosslinking the dextran shell with epichlorohydrin significantly decreased C3 Opsonization and uptake by mouse peritoneal macrophages. Crosslinked nanoworms further functionalized with poly(ethylene glycol) (PEG) or with PEG-antibody (~160 IgG molecules per particle) did not show an increase in C3 Opsonization and peritoneal macrophage uptake in vitro. Following tail vein injection into mice, plain crosslinked nanoworms and PEGylated crosslinked nanoworms showed very low C3 Opsonization and mouse leukocyte uptake. However, antibody-decorated crosslinked nanoworms showed significant C3 Opsonization and high level of complement-dependent uptake by leukocytes in mice. Decreasing the number of conjugated antibodies to 46 IgG molecules per particle significantly reduced C3 Opsonization and leukocyte uptake. Using fresh mouse lepirudin plasma rather than serum showed better correlation with C3 Opsonization in vivo. The reason for this difference could be related to the known instability of complement classical pathway in mouse sera. Our data illustrate that fine-tuning in nanoparticle surface functionalization with antibodies is required to avoid excessive complement activation and complement-mediated immune uptake in mice, and raise issues with in vitro immunological assays of nanomedicines intended to mimic in vivo conditions.

  • in vitro and in vivo differences in murine third complement component c3 Opsonization and macrophage leukocyte responses to antibody functionalized iron oxide nanoworms
    Frontiers in Immunology, 2017
    Co-Authors: Guankui Wang, Seyed Moein Moghimi, James I Griffin, Swetha Inturi, Barbara Brenneman, Nirmal K Banda, Michael V Holers, Dmitri Simberg
    Abstract:

    Balancing surface functionalization and low immune recognition of nanomedicines is a major challenge. Opsonization with the third component of the complement protein (C3) plays a major role in immune cell recognition of nanomedicines. We used dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs) to study the effect of surface functionalization on C3 Opsonization in mouse serum and subsequent macrophage/leukocyte recognition in vitro as well as on intravenous injection into mice. Previously, we found that in mouse serum, SPIO NWs became opsonized with C3 via complement lectin pathway. Crosslinking the dextran shell with epichlorohydrin significantly decreased C3 Opsonization and uptake by mouse peritoneal macrophages. Crosslinked nanoworms (NWs) further functionalized with polyethylene glycol (PEG) or with PEG-antibody (Ab) (~160 IgG molecules/particle) did not show an increase in C3 Opsonization and peritoneal macrophage uptake in vitro. Following tail vein injection into mice, plain crosslinked NWs and PEGylated crosslinked NWs showed very low C3 Opsonization and mouse leukocyte uptake. However, Ab-decorated crosslinked NWs showed significant C3 Opsonization and high level of complement-dependent uptake by leukocytes in mice. Decreasing the number of conjugated Abs to 46 IgG molecules/particle significantly reduced C3 Opsonization and leukocyte uptake. Using fresh mouse lepirudin plasma rather than serum showed better correlation with C3 Opsonization in vivo. The reason for this difference could be related to the known instability of complement classical pathway in mouse sera. Our data illustrate that fine-tuning in nanoparticle surface functionalization with Abs is required to avoid excessive complement activation and complement-mediated immune uptake in mice, and raise issues with in vitro immunological assays of nanomedicines intended to mimic in vivo conditions.

Roberto Cevenini - One of the best experts on this subject based on the ideXlab platform.

  • Phagocytosis of Treponema pallidum and reactive oxygen species production by isolated rat Kupffer cells
    Medical Microbiology and Immunology, 2003
    Co-Authors: Antonella Marangoni, Rita Aldini, Massimo Guardigli, Vittorio Sambri, Lorenzo Giacani, Marco Montagnani, Aldo Roda, Roberto Cevenini
    Abstract:

    The in vitro phagocytosis of viable Treponema pallidum subsp. pallidum by isolated rat Kupffer cells, studied by immunofluorescence staining of Kupffer cells-associated bacteria, showed that ingestion of live, unopsonized treponemes was slow: in fact, Kupffer cells started to be positive 1 h after infection, when only 4% of the cells presented small round fluorescent inclusion-like bodies. Thereafter, the number of positive cells progressively increased with time: 7%, 17%, 36%, and 69% of Kupffer cells were positive, respectively, 2, 4, 6 and 8 h after infection. Opsonization of T. pallidum with human immune serum did not substantially modify the percentage (8%) of Kupffer cells ingesting T. pallidum 1 h after infection, whereas Opsonization significantly ( P

Alexander M Hirschl - One of the best experts on this subject based on the ideXlab platform.

  • helicobacter pylori urease significantly reduces Opsonization by human complement
    The Journal of Infectious Diseases, 1998
    Co-Authors: Elmar Rokita, Athanasios Makristathis, Elisabeth Presterl, M Rotter, Alexander M Hirschl
    Abstract:

    The role of Helicobacter pylori urease in Opsonization by human complement was investigated. H. pylori wild type strain N6 and isogenic mutants lacking either the large urease subunit (UreB) or an accessory urease protein (UreG) were incubated with different sera. C3b bound to the bacteria was measured by specific staining and flow cytometry. As compared with Opsonization of N6 and the UreG-lacking mutant, Opsonization of the UreB-lacking mutant was significantly increased after incubation with sera from both H. pylori uninfected (P<.001) or infected (P<.05) persons. However, when sera from uninfected persons were used, effective Opsonization of this mutant proved to be dependent mainly on the classical pathway of complement activation. Irrespective of the serum used, Opsonization values were very low after selective inactivation of the classical or the alternative pathway. Reduced Opsonization of the urease-expressing strains could, to some extent, result from degradation of bound C3b.

  • Helicobacter pylori Urease Significantly Reduces Opsonization by Human Complement
    The Journal of Infectious Diseases, 1998
    Co-Authors: Elmar Rokita, Athanasios Makristathis, Elisabeth Presterl, Manfred L. Rotter, Alexander M Hirschl
    Abstract:

    The role of Helicobacter pylori urease in Opsonization by human complement was investigated. H. pylori wild type strain N6 and isogenic mutants lacking either the large urease subunit (UreB) or an accessory urease protein (UreG) were incubated with different sera. C3b bound to the bacteria was measured by specific staining and flow cytometry. As compared with Opsonization of N6 and the UreG-lacking mutant, Opsonization of the UreB-lacking mutant was significantly increased after incubation with sera from both H. pylori uninfected (P