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Journal Article

ACTIVATION AND INHIBITION OF IgG MEDIATED COMPLEMENT FIXATION BY STAPHYLOCOCCAL PROTEIN A

01 Aug 1970-Clinical and Experimental Immunology (Clin Exp Immunol)-Vol. 7, Iss: 2, pp 211-220
TL;DR: The dual effect of protein A might be explained by its ability to arrange γ-globulin molecules in a way initiating the complement cascade and inhibition of Fc mediated complement activation by steric hindrance when added in excess.
Abstract: Staphylococcal protein A, when added to fresh human, guinea-pig, dog or pig serum, caused a marked depletion of complement. This complement consumption, further studied in the human system, was noted only in γglobulin excess. The consumption of individual complement components indicated an activation mechanism similar to the one induced by aggregated human γ-globulin; i.e. a marked depletion of early-acting components. The activation was time- and temperature-dependent. Almost no complement activation was seen using fresh serum from a patient with agammaglobulinaemia. Inhibition of complement activation was noted when protein A was added at equivalence of precipitation or in excess. The dual effect of protein A might be explained by (I) its ability to arrange γ-globulin molecules in a way initiating the complement cascade and (II) inhibition of Fc mediated complement activation by steric hindrance when added in excess. Possible roles of protein A in the pathogenesis of staphylococcal infections are discussed.
Citations
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Journal ArticleDOI
TL;DR: Protein A has proven useful for the study of antigens and receptors on the surface of intact cells, and for the detection of antibody-secreting cells, so the use of protein A is now the method of choice for many preparative and analytical purposes in immunology.

936 citations

Book ChapterDOI
TL;DR: This chapter discusses the occurrence, properties, applications, biological activity, and potential significance of Ig receptors produced mainly by staphylococci and streptococci, more broadly classified more broadly as Ig receptors.
Abstract: Publisher Summary Several hundred strains of staphylococci and related organisms have been tested for the production of cell surface and/or extracellular SPA. Techniques for detecting the cell-bound protein include agglutination of erythrocytes sensitized with SPA-reactive antibody. Results have demonstrated the presence of extracellular as well as cell-bound SPA and implied that SPA on the membrane had easy access to Ig molecules in the fluid phase or bound to cell-surface antigens in such a way that the Fc region could interact with SPA receptors. Indeed, studies have shown that SPA is located primarily on the surface of Cowan strain I and is linked covalently to the peptidoglycan portion of the membrane. Studies on biosynthesis have been carried out in strains that produce cell-bound, as well as extracellular SPA (e.g., Cowan I) or only the extracellular product. The physicochemical properties of SPA prepared by lysostaphin treatment of Cowan strain I are summarized. The high frictional ratio (2:1) and intrinsic viscosity (29 ml/gm) compared to values normally obtained for globular proteins (1.1- 1.25 and 3-4 mg/gm, respectively) suggest that SPA is a relatively elongated molecule. The molecular weight of 42,000 is the average of several determinations and is the generally accepted value. This compares to the molecular weight of 29,500 found in the most active fraction obtained after chromatography of heat-extracted material. This chapter discusses the occurrence, properties, applications, biological activity, and potential significance of Ig receptors produced mainly by staphylococci and streptococci. Although they act primarily as Fc receptors, for this discussion they have been classified more broadly as Ig receptors. This is because SPA displays secondary binding activity localized in the Fab region of certain species and classes of Ig, and this has been reported to be the sole type of activity associated with polyclonal human IgE.

578 citations

Journal ArticleDOI
TL;DR: Data are presented showing that SpA is a highly efficient mitogen for human peripheral B lymphocytes, with no detectable activity for T lymphocyte, in order to achieve optimal stimulating conditions SpA should be presented to the lymphocytes on an insoluble matrix.
Abstract: Protein A from Staphylococcus aureus (SpA) is known to bind to the Fc region of most mammalian IgG classes. In the present article data are presented showing that SpA is a highly efficient mitogen for human peripheral B lymphocytes, with no detectable activity for T lymphocytes. In order to achieve optimal stimulating conditions SpA should be presented to the lymphocytes on an insoluble matrix, such as the SpA-positive bacteria themselves or SpA covalently attached to Sephadex or Sepharose beads. Using such conditions SpA is equivalent with regard to stimulatory capacity for B lymphocytes as phytohemagglutinin is for the human T lymphocytes. Specificity controls proved beyond doubt that SpA and not any other contaminating product is the B cell mitogen. It is concluded that SpA as an inducer of human B lymphocyte division might serve as a highly useful assay in the clinical assessment of B lymphocyte function. It should also be a suitable tool in the fine analysis of B lymphocyte activation via the specific interactions with surface IgG molecules.

252 citations

Journal ArticleDOI
TL;DR: Results clearly indicate that SpA is a virulence factor of S. aureus in murine septic arthritis and the wild-type strain gave rise to more severe arthritis and higher mortality than the isogenic spa mutant strain DU5873.

184 citations

Journal Article
TL;DR: In this paper, protein A extracted from Staphylococcus aureus inhibited phagocytosis of Escherichia coli in in vitro phagocyte-systems.
Abstract: Strains of Staphylococcus aureus possessing large amounts of protein A tended to resist phagocytosis more than strains that contain lesser amounts or none of this protein. Protein A extracted from S. aureus inhibited phagocytosis of both S. aureus and Escherichia coli in in vitro phagocytosis systems. The antiphagocytic effect was produced by nonspecific reaction of protein A with the Fc piece of γG globulin.

152 citations

References
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Journal Article
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.

289,852 citations

Journal Article
TL;DR: It appears that anti-protein A reactivity is confined to γG-1, γ G-2 and γE4 molecules, and the presence of protein A-reactive sites is confirmed.
Abstract: The reaction between staphylococcal protein A and human γG globulin, which is known to be mediated by structures on the Fc part of the heavy chains, was studied qualitatively using 68 isolated γG myeloma globulins. Twenty-one myeloma globulins of subgroups γG-1, γG-2 and γG-4 gave a precipitin reaction with protein A. The 35 remaining meyloma globulins of these subgroups all inhibited this reaction, indicating the presence of protein A-reactive sites. Twelve γG-3 myeloma globulins did not precipitate or inhibit the precipitation; two showed slight inhibition that could be attributed to background γG. It thus appears that anti-protein A reactivity is confined to γG-1, γG-2 and γG-4 molecules.

468 citations

Journal Article
TL;DR: Protein A may provide a useful tool in the study of the evolution of γG globulin and a comparison of patterns of reactivity between protein A and isolated human rheumatoid factors showed that in the majority of instances different specificities were involved.
Abstract: The reaction between protein A of staphylococci and the Fc portion of γG globulins has been studied using representative sera and isolated γ globulins from species representing seven classes and 30 orders of living vertebrates. No reactions with immunoglobulins derived from either the primitive or later evolving fishes were noted. No reactions were recorded among Amphibia and Reptilia as well as all birds tested, except with serum from the primitive flightless bird Rhea americana . All members of the class Mammalia, including egg-laying monotremes, showed reactions with protein A except for the American oppossum. A comparison of patterns of reactivity between protein A and isolated human rheumatoid factors showed that in the majority of instances different specificities were involved. Protein A may provide a useful tool in the study of the evolution of γG globulin.

351 citations

Journal ArticleDOI
22 Oct 1965-Science
TL;DR: It is concluded that a single molecule of 19S antibody in combination with antigen at the cell surface is sufficient to bind one molecule of Ć1a, the activated first component of complement.
Abstract: The mechanism of complement fixation on cell surfaces by whole antiserums, and by 19S and 7S fractions has been studied with a new comple-ment-fixation test. This test is based on the fixation and transfer of the activated first component of complement (C1a). We have concluded that a single molecule of 19S antibody in combination with antigen at the cell surface is sufficient to bind one molecule of C1a. For 7S antibodies at least two molecules in close proximity at the cell surface are required to fix one molecule of C1a.

316 citations

Journal ArticleDOI
TL;DR: These experiments support the hypothesis that certain biological effects induced by endotoxins may be mediated via the C' system, and may account for some of the known similarity in the reactivities evoked by endotoxic lipopolysaccharide, zymosan, or preformed immune complexes in vivo.
Abstract: Large amounts of each C'3, C'5, C'6, C'7, C'8, and C'9 were consumed when guinea pig serum was incubated with endotoxic lipopolysaccharide, zymosan, or preformed immune complexes. Since these C' components subserve several of the biological activities which follow the injection of endotoxins into experimental animals, these experiments support the hypothesis that certain biological effects induced by endotoxins may be mediated via the C' system, and may account for some of the known similarity in the reactivities evoked by endotoxins and immune complexes in vivo.

276 citations