title: Staphylococcal exotoxins exert proinflammatory effects through inhibition of eosinophil apoptosis, increased surface antigen expression (CD11b, CD45, CD54, and CD69), and enhanced cytokine-activated oxidative burst, thereby triggering allergic inflammatory reactions.
abstract: BACKGROUND
  Staphylococcus aureus colonization of the skin represents a potent trigger factor of atopic dermatitis. Our previous studies demonstrated that in atopic dermatitis eosinophil apoptosis is significantly delayed.
  
  
  OBJECTIVE
  We sought to investigate the effect of staphylococcal exotoxins (SETs) on eosinophil apoptosis and functional activities.
  
  
  METHODS
  Apoptotic eosinophils were investigated by determining their hypodiploid DNA peak. Eosinophil surface-antigen expression and intracellular production of hydrogen peroxide were assessed by means of flow cytometric analysis and respiratory burst by lucigenin-dependent chemiluminescence.
  
  
  RESULTS
  The SETs SEA, SEB, SEC, and toxic shock syndrome toxin 1 significantly inhibited eosinophil apoptosis in a manner comparable with that of high concentrations of IL-3. The LPS inhibitor polymyxin B was found to significantly inhibit LPS-mediated, but not SET-mediated, inhibition of apoptosis. Neither SETs nor LPS was able to modulate eosinophil surface expression of CD9, CD11a, CD16, CD40, CD44, or CD63. However, 24- and 48-hour incubation with all SETs, but not with LPS, significantly upregulated expression of CD11b and CD45 in a manner similar to that of IL-3, whereas dexamethasone induced a downregulation. Moreover, all SETs resulted in a significant upregulation of CD54 after 24 hours but not after 48 hours. Interestingly, CD69 was upregulated by means of IL-3 and SEB only. Neither direct stimulation of eosinophils nor 24-hour incubation with SETs or stimulation with SETs after a 24-hour prestimulation with IL-3, IL-5, or GM-CSF resulted in a significant extracellular production of reactive oxygen species or in a significant production of intracellular hydrogen peroxide. However, SEB and toxic shock syndrome toxin 1 were able to enhance cytokine-induced respiratory burst.
  
  
  CONCLUSIONS
  Taken together, our data demonstrate that SETs may modulate the course of the allergic inflammatory response through modulation of potent eosinophil effector functions. This may be of particular importance in atopic dermatitis, in which the skin is regularly colonized with SET-producing S aureus.
authors.affiliation: Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wedi
authors.forename: Dorothea
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Tanja
authors.initials: T
authors.lastname: Stünkel
authors.forename: Kristine
authors.initials: K
authors.lastname: Breuer
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapp
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005098:Exotoxins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D016897:Respiratory Burst; D013211:Staphylococcus aureus; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001427:Bacterial Toxins; D016207:Cytokines; D005098:Exotoxins; D018799:Intercellular Adhesion Molecule-1; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D016177:Macrophage-1 Antigen; D000099192:CD69 Antigens