Mechanism of activation of human basophils by Staphylococcus aureus Cowan 1.
We investigated the capacity of Staphylococcus aureus Cowan 1 and S. aureus Wood 46 to induce histamine release from human basophils in vitro. S. aureus Cowan 1 (10(5) to 10(7)/ml), which synthesizes protein A (Staph A), stimulated the release of histamine from basophils, whereas S. aureus Wood 46 (10(5) to 2 X 10(7)/ml), which does not synthesize Staph A, did not induce histamine secretion. Soluble Staph A (10(-3) to 10 micrograms/ml), but not staphylococcal enterotoxin A, induced histamine secretion from human basophils. Staph A binds through its classical site to the Fc region of human immunoglobulin G (IgG) and through its alternative site to the Fab portion of the different human immunoglobulins. Hyperiodination of Staph A, which destroys over 90% of the original Fc reactivity without altering the Fab-binding site, did not alter the ability of the protein to induce histamine release. The stimulating effect of Staph A was dose dependently inhibited by preincubation with human polyclonal IgG (0.3 to 100 micrograms/ml) and a human monoclonal IgM (0.3 to 100 micrograms/ml) which have F(ab')-Staph A reactivity. In contrast, rabbit IgG, which possesses only Fc-Staph A reactivity, and a Staph A-unreactive human monoclonal IgM did not inhibit Staph A activity. Similar results were obtained with intact S. aureus Cowan 1. Preincubation with either Staph A or anti-IgE (rabbit anti-Fc epsilon) resulted in complete desensitization to a subsequent challenge with the homologous stimulus. Staph A and anti-IgE induced partial cross-densensitization to the heterologous stimulus. Cells preincubated with anti-IgG (rabbit anti-Fc gamma) lost a small but significant part of their ability to release with Staph A but did not lose their response to anti-IgE. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and Staph A. When basophils from which IgE had been dissociated were incubated with human polyclonal IgE, they regained their ability to induce histamine in response to Staph A and anti-IgE. In contrast, two monoclonal IgEs which do not bind to Staph A did not restore the basophil responsiveness to Staph A. Furthermore, there was complete cross-desensitization between soluble Staph A and S. aureus Cowan 1, while cells desensitized to S. aureus Wood 46 released normally with Staph A and S. aureus Cowan 1.(ABSTRACT TRUNCATED AT 400 WORDS)
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001491:Basophils / Q000378:metabolism*; D001665:Binding Sites; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D013205:Staphylococcal Protein A; C026066:enterotoxin A, Staphylococcal