No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
A Protein in the Cell Wall of Helicobactor Pylori Binds Human IgG Deprived of Sugar Chains
Abstract
We found a protein binding non-antibody human IgG in Helicobactor pylori cell wall, when the IgG was enzymically deglycosylated. The protein had the amino acid sequence AEDGAHVAFM. IgG of H. pylori patients also bound to the protein and the IgG lost the sugar chain structure reactivities. These findings indicate that H. pylori binds human IgG without the sugar chains on its cell wall and suggest that H. pylori infection has a relation to the human IgG deglycosylation. - Helicobactor pylori; human IgG; glycosylation; a protein of the cell wall
Helicobacter pylori, a gram-negative spiral-shaped bacterium, specifically colonizes the stomachs of humans. Once established in this harsh ecological niche, it remains there virtually for the entire life of the host. To date, numerous virulence factors responsible for gastric colonization, survival, and tissue damage have been described for this bacterium. Nevertheless, a critical feature of H. pylori is its ability to establish a long-lasting infection. In fact, although good humoral (against many bacterial proteins) and cellular responses are observed, most infected persons are unable to eradicate the infection. A large body of evidence has shown that the interaction between H. pylori and the host is very complex. In addition to the effect of virulence factors on colonization and persistence, binding of specialized bacterial proteins, known as receptins, to certain host molecules (ligands) could explain the success of H. pylori as a chronically persisting pathogen. Some of the reported interactions are of high affinity, as revealed by their calculated dissociation constant. This review examines the binding of host proteins (serum and extracellular matrix proteins) to H. pylori and considers the significance of these interactions in the infectious process. A more thorough understanding of the kinetics of these receptin interactions could provide a new approach to preventing deeper tissue invasion in H. pylori infections and could represent an alternative to antibiotic treatment.
The protein composition of purified outer membranes of 47 Escherichia coli strains was examined by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis. Of 33 encapsulated strains, all contained an outer membrane protein distinguishable from previously reported proteins. The 14 non-encapsulated strains with one exception lacked this protein. Because of its apparent association with encapsulation (K antigen) we have named it K protein. The protein was purified nearly to homogeneity by chromatography in the presence of detergents, and its composition was determined. Its amino acid composition does not differ significantly from that reported for protein I, another E. coli major outer membrane protein. Furthermore, the N-terminal amino acid sequence of protein K indicates that it is related to protein I.
Complexes between IgG or the Fc fragment of IgG and protein A from S. aureus activate the serum complement system in a manner which is entirely analogous to complement activation by antigen-antibody complexes. Thus C1,C4,C2,C3,C5,C6,C8 and C9 were found to be depleted on addition of protein A to serum. The alternate complement pathway was also activated on addition of protein A to serum. Consumption of the components and the C3 proactivator varied with the dose of protein A and the same dose response curve was obtained for activation of both pathways in serum. Maximal activation occurred with the same dose of protein A. Protein A was found to be able to inhibit binding of by IgG1 or the Fc fragment of IgG1, indicating that the complement activating site and protein A binding site are sterically close. Finally, it has been found that erythrocytes passively coated with protein A lyse in fresh normal human or guinea pig serum.
Heat or alkali-aggregated IgG was found to inhibit C2 production by monocytes, whereas chemically cross-linked IgG and antigen-antibody complexes stimulated C2 synthesis. Chemically cross-linked IgG was shown to inhibit monocyte EA-rosette formation presumably because it blocked monocyte Fc receptors. Furthermore stimulation of C2 synthesis was limited to polymers of the IgG1 and IgG3 subclasses. In contrast, heat-aggregated IgG failed to inhibit monocyte EA-rosette formation significantly, and all the heat-aggregated IgG subclasses inhibited C2 production. It therefore appears that physically aggregated IgG does not bind effectively to Fc receptors. As the effects of physically aggregated IgG C2 production are similar to those of the hydrophobic proteins casein and alkali-denatured human serum albumin (HSA), it is suggested that hydrophobic residues in the aggregates bind preferentially to the lipid component of the cell membrane.
Several techniques have been proposed to diagnose H. pylori infection based either on the direct or indirect detection of the bacteria. [table: see text] The current direct methods are performed on biopsy specimens obtained at endoscopy. Histological examination must always be performed because in addition to H. pylori detection it allows observation of the lesions present. Culture, while more demanding in terms of transport conditions, is a sensitive technique which is worthwhile when the patient might be treated with antibiotics to which the bacteria may be resistant. PCR has been more recently introduced and exhibits a good sensitivity and specificity. Rapid tests, such as the rapid urease test and examination of a Gram stained biopsy smear, are convenient and cheap but of lower sensitivity. Indirect methods are based either on the serological IgG response or the labelled urea breath test. Both are sensitive. The breath test is especially adapted to post-treatment control while serology is of interest for screening patients and epidemiological studies. New techniques have recently been proposed but are not yet applicable to routine diagnosis: detection of H. pylori in faeces by culture or PCR; detection of IgG antibodies in saliva or urine.
Studies conducted in Europe suggest an association between IgG glycosylation abnormalities and rheumatoid arthritis (RA). Glycosylation abnormalities have been shown in other inflammatory diseases such as tuberculosis, systemic lupus erythematosus (SLE) and Crohn's disease. These observations led us to study glycosylation abnormalities among patients with RA and healthy controls in the tropics (sub-Saharan Africa). Using a lectin binding assay, we found that glycosylation differences were present in both groups when compared with British rheumatoid and healthy controls. This suggests that IgG glycosylation abnormalities may occur in association with chronic infections in the tropics.
This paper outlines a model describing how animals adapt to a particular circumstance. This model is based on observations that animals learn behaviors that best fit a circumstance, and that the adapted animals then select the most suitable behavior that minimizes their psychological energy usage. The model consists of behavioral memory units and their network connections. By using the model, various animal disadaptations can be analyzed and the antibody-production system can be clearly explained as an adaptation. Finally, it is proposed that simulation of the model can be performed on a computer.
A specific dopamine 2 receptor antagonist, (-)sulpiride, induced an anti-depressive behavior, climbing, in mice forced to swim for 6 h after the injection. The effective fraction was divided from the mouse serum using an ion exchanger and an ultra filtration method. This fraction contained fibrinopeptide A. A peptide synthesized according to the primary 6-amino acid sequence (TDTEDK) of fibrinopeptide A also remarkably increased the behavior. The present findings clearly indicate that a peptide with TDTEDK showed anti-depressive activity.
We investigated the late effects of serotonergic drugs on mouse forced swimming and found that serotonin 1A antagonist NAN-190 hydrobromide (NAN-190) and serotonin 2 agonist R(-)-DO1 hydrochloride (DO1) increase the typical anti-depressive behavior climbing 6 hours after the intraperitoneal injection. With the use of ion exchanger, ultra filtration and chemical extraction methods, a substance having remarkable anti-depressive activity on mouse forced swimming was extracted from the serums of the mice treated with the drugs. The substance was strongly suggested to be a glycolipid having a specific sugar chain structure GalNAcalpha1-3GalNAc in its terminal. In fact, globopentaosylceramide, another glycolipid having the structure in the terminal also showed marked anti-depressive activity on mouse forced swimming, but globotetraosylceramide lacking the sugar chain structure did not. The GalNAcalpha1-3GalNAc-lipid reactivity in the serum and typical anti-depressive behavior climbing increased corresponding to the doses of NAN-190 and DO1. These findings clearly indicate that the terminal structure GalNAcalpha1-3GalNAc has the essential role in the anti-depressive activity of globopentaosylceramide, and that serotonin 1A antagonism and serotonin 2 agonism increase the production of an anti-depressive glycolipid having the terminal structure in mouse serum.