Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps.
BACKGROUND
Recent studies have revealed that Staphylococcus aureus and its components participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyps.


OBJECTIVE
We sought to determine whether staphylococcal protein A (SpA) from S aureus regulated cellular responses in nasal polyps, especially when coupled to immunoglobulins in immune complexes (ICs).


METHODS
Dispersed nasal polyp cells (DNPCs) or peripheral blood monocytes were cultured in vitro with SpA in the presence or absence of IgG, and IL-5, IL-13, IFN-γ, IL-17A, and IL-10 levels were measured in the supernatants. The effect of SpA exposure on staphylococcal enterotoxin B-induced cytokine production by DNPCs in the presence and absence of IgG, IgA, and autologous serum was also examined.


RESULTS
Exposure to SpA induced DNPCs to produce significantly higher IL-10, IL-13, and IL-17A levels than DNPCs without SpA, although the magnitude of the IL-17A increase was less than that of IL-10 and IL-13. SpA induced IL-10 production mainly from adherent DNPCs, and this was significantly enhanced in the presence of IgG; similar results were observed in peripheral blood monocytes. IC formation between SpA and IgG (SpA-IgG ICs) was confirmed by using native polyacrylamide gel electrophoresis. SpA-IgG ICs, but not SpA alone, almost completely suppressed staphylococcal enterotoxin B-induced IL-5, IL-13, IFN-γ, and IL-17A production by DNPCs; similar inhibition was observed in DNPCs treated with SpA in the presence of either IgA or autologous serum.


CONCLUSIONS
Our results suggest that SpA can regulate the pathogenesis of enterotoxin-induced inflammation in patients with chronic rhinosinusitis with nasal polyps through coupling to immunoglobulins.
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mokano@cc.okayama-u.ac.jp.
Mitsuhiro
M
Okano
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tazuko
T
Fujiwara
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shin
S
Kariya
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takenori
T
Haruna
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takaya
T
Higaki
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yasuyuki
Y
Noyama
Department Otorhinolaryngology, Kagawa Rosai Hospital, Marugame, Japan.
Sei-ichiro
S
Makihara
Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
Kengo
K
Kanai
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kazunori
K
Nishizaki
D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000096:biosynthesis*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000276:immunology / Q000473:pathology / Q000601:surgery; D009298:Nasal Polyps / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D061251:Primary Cell Culture; D012220:Rhinitis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D012852:Sinusitis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013205:Staphylococcal Protein A / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D004768:Enterotoxins; C508717:IL17A protein, human; C508599:IL5 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D013205:Staphylococcal Protein A; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma
Chronic rhinosinusitis with nasal polyps; Staphylococcus aureus; cytokines; enterotoxins; immune complexes; immune evasion; immunoglobulins; staphylococcal protein A