Wedi Bettina, Wieczorek Dorothea, Stünkel Tanja, Breuer Kristine, Kapp Alexander
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
J Allergy Clin Immunol. 2002 Mar;109(3):477-84. doi: 10.1067/mai.2002.121702.
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.
We sought to investigate the effect of staphylococcal exotoxins (SETs) on eosinophil apoptosis and functional activities.
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.
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.
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.
皮肤金黄色葡萄球菌定植是特应性皮炎的一个有力触发因素。我们之前的研究表明，在特应性皮炎中嗜酸性粒细胞凋亡显著延迟。
我们试图研究葡萄球菌外毒素（SETs）对嗜酸性粒细胞凋亡和功能活性的影响。
通过测定亚二倍体DNA峰来研究凋亡嗜酸性粒细胞。通过流式细胞术分析评估嗜酸性粒细胞表面抗原表达和过氧化氢的细胞内产生，并通过光泽精依赖性化学发光法评估呼吸爆发。
SETs中的SEA、SEB、SEC和中毒性休克综合征毒素1以与高浓度IL-3相当的方式显著抑制嗜酸性粒细胞凋亡。发现LPS抑制剂多粘菌素B能显著抑制LPS介导的而非SET介导的凋亡抑制。SETs和LPS均不能调节嗜酸性粒细胞表面CD9、CD11a、CD16、CD40、CD44或CD63的表达。然而，与所有SETs孵育24小时和48小时，但不与LPS孵育，以与IL-3相似的方式显著上调CD11b和CD45的表达，而地塞米松则诱导下调。此外，所有SETs在24小时后导致CD54显著上调，但在48小时后未上调。有趣的是，只有IL-3和SEB能上调CD69。无论是直接刺激嗜酸性粒细胞，还是与SETs孵育24小时，或在用IL-3、IL-5或GM-CSF预刺激24小时后用SETs刺激，均未导致活性氧的显著细胞外产生或细胞内过氧化氢的显著产生。然而，SEB和中毒性休克综合征毒素1能够增强细胞因子诱导的呼吸爆发。
综上所述，我们的数据表明SETs可能通过调节嗜酸性粒细胞的有效效应功能来调节过敏性炎症反应的进程。这在特应性皮炎中可能尤为重要，因为在特应性皮炎中皮肤经常被产生SETs的金黄色葡萄球菌定植。
