Effect of immunoglobulin class and affinity on the initiation of complement-dependent damage to liposomal model membranes sensitized with dinitrophenylated phospholipids

Six, Howard R.; Uemura, Keiichi; Kinsky, Stephen C.

doi:10.1021/bi00744a034

Cited by 78 publications

(42 citation statements)

References 16 publications

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“…These observations brought into question the hostprotective role of anti-/! gingivalis antibodies in periodontai disease, since the efficacy of a variety of immunologic host defense mechanisms, such as complement activation (10,36), immune elitnnination (1) and virus neutralization (2), are affected by the avidity of the participating antibody. Thus, although periodontai patiehts frequently have higher anii-P. gingivalis immunoglob-ulin G (IgG) titers than normal subjects (8), this antibody tnay be of low protective value.…”

mentioning

confidence: 99%

Avidity and titer of immunoglobulin G subclasses to Porphymmonas gingivalis in adult periodontitis patients

Lopatin

Blackburn

1992

Oral Microbiology and Immunology

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The relative avidity and titer of antibodies representing the 4 immunoglobulin G (IgG) subclasses (IgG1-4) reactive with Porphyromonas gingivalis, P. gingivalis-lipopolysaccharide (-LPS), streptokinase (SK) and tetanus toxoid (TT) in the sera of patients having adult periodontitis and of healthy controls were measured. Patient antibody titers to P. gingivalis and P. gingivalis-LPS were found to be significantly elevated for IgG, IgG1 (no P. gingivalis-LPS antibodies) and IgG2. The predominant antibody response to P. gingivalis and P. gingivalis-LPS occurred in the IgG2 subclass. When the relative avidity of the antibodies to P. gingivalis and P. gingivalis-LPS were examined, no significant differences between control and patient sera could be identified. However, anti-P. gingivalis and P. gingivalis-LPS antibodies were found to possess significantly lower relative avidity than either SK or TT antibodies. The IgG1 subclass antibodies to P. gingivalis, SK and TT all appeared to be of high relative avidity. In contrast, anti-P. gingivalis and P. gingivalis-LPS of the IgG2 subclass were of significantly lower relative avidity. Since the predominant humoral response to P. gingivalis occurs in the IgG2 subclass, the low relative avidity of these antibodies predominates in measurements of whole serum activity.

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mentioning

confidence: 99%

Avidity and titer of immunoglobulin G subclasses to Porphymmonas gingivalis in adult periodontitis patients

Lopatin

Blackburn

1992

Oral Microbiology and Immunology

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“…To prepare 25 mM Mtx solution, dry Mtx was added to a solution containing 10 mM CF and 1.25% NaHCO3. Dioleoyl, dipalmitoyl, and distearoyl phosphatidylcholines (Ole2-PtdCho, Pam2-PtdCho, and Ste2-PtdCho, respectively) and DNP coupled through a six-carbon spacer to phosphatidylethanolamine (DNP-cap-PtdEtn) (20) (10). In some experiments, heat-aggregated IgG from unimmunized rabbits or a combination of metabolic inhibitors (0.1% NaN3 and 50 mM 2-deoxy-D-glucose) was added 30 min prior to the antibody.…”

mentioning

confidence: 99%

Receptor-mediated endocytosis of antibody-opsonized liposomes by tumor cells.

Leserman¹,

Weinstein²,

Blumenthal³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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Specific receptor-mediated delivery of the contents of small, sonicated liposomes was studied with three murine tumor cell types: an IgG Fc receptor-negative nonphagocytic line (ETA); an Fc receptor-positive phagocytic line (P388D1) and an Fc receptor-positive nonphagocytic line (P388) The liposomes (formed from phosphatidylcholines, cholesterol, and dinitrophenyl-substituted phosphatidylethanolamine) contained carboxyfluorescein as a fluorescent marker and methotrexate as a pharmacologic agent. Binding and internalization of the liposomes were observed by fluorescence microscopy and measured by flow microfluorometry. The hapten-derivatized lipid was used as a binding point on the liposome for the antibzy-combining site of the immunogloburin.

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“…Azide-covered Hp would be selectively targeted via Staudinger ligation with phosphine probes conjugated to immune stimulants (Figure 1). These immune stimulants, such as 2,4-dinitrophenyl (DNP) [11] and the galactosyl-(1,3)-galactose (alpha-Gal) [12] epitope, would trigger host immune cells to destroy labeled cells (Figure 1). Indeed, delivery of these immune stimulants to a variety of bacteria, viruses, and cancer cells by other targeting means has initiated selective immune killing both in vitro and in vivo [13] .…”

Section: Introductionmentioning

confidence: 99%

Recruiting the Host's Immune System to Target Helicobacter pylori's Surface Glycans

2013

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Due to the increased prevalence of bacterial strains that are resistant to existing antibiotics, there is an urgent need for new antibacterial strategies. Bacterial glycans are an attractive target for new treatments, as they are frequently linked to pathogenesis and contain distinctive structures that are absent in humans. We set out to develop a novel targeting strategy based on surface glycans present on the gastric pathogen Helicobacter pylori (Hp). In this study, metabolic labeling of bacterial glycans with an azide-containing sugar allowed selective delivery of immune stimulants to azide-covered Hp. We established that Hp’s surface glycans are labeled by treatment with the metabolic substrate peracetylated N-azidoacetylglucosamine (Ac4GlcNAz). By contrast, mammalian cells treated with Ac4GlcNAz exhibit no incorporation of the chemical label within extracellular glycans. We further demonstrated that the Staudinger ligation between azides and phosphines proceeds under acidic conditions with only a small loss of efficiency. We then targeted azide-covered Hp with phosphines conjugated to the immune stimulant 2,4-dinitrophenyl (DNP), a compound capable of directing a host immune response against these cells. Finally, we report that immune effector cells catalyze selective damage in vitro to DNP-covered Hp in the presence of anti-DNP antibodies. The technology reported herein represents a novel strategy to target Hp based on its glycans.

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Effect of immunoglobulin class and affinity on the initiation of complement-dependent damage to liposomal model membranes sensitized with dinitrophenylated phospholipids

Abstract: The principal goal of this investigation was to examine some of the factors that determine how much antigen must be incorporated into liposomal model membranes to render them susceptible to immune damage by the classical complement pathway. Liposomes were actively sensitized

Cited by 78 publications

References 16 publications

Avidity and titer of immunoglobulin G subclasses to Porphymmonas gingivalis in adult periodontitis patients

Avidity and titer of immunoglobulin G subclasses to Porphymmonas gingivalis in adult periodontitis patients

Receptor-mediated endocytosis of antibody-opsonized liposomes by tumor cells.

Recruiting the Host's Immune System to Target Helicobacter pylori's Surface Glycans

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