Miller E J, Nagao S, Carr F K, Noble J M, Cohen A B
Department of Biochemistry, University of Texas Health Center, Tyler 75710-2003, USA.
Inflamm Res. 1996 Aug;45(8):386-92. doi: 10.1007/BF02252933.
Since Staphylococcus aureus is an important human pathogen, and infection of the lungs is characterized by neutrophil infiltration we studied the role of a staphylococcal toxin, enterotoxin A (SEA) on the synthesis and secretion of IL-8 by human alveolar macrophages. As SEA concentration was increased, the IL-8 accumulation in the macrophage conditioned medium increased. The concentration of mRNA encoding IL-8 was also elevated in the macrophage in response to increases in SEA concentration. Although the monocytic cell line U937 was able to respond to SEA and secrete IL-8, treatment with PMA prior to SEA stimulation increased the IL-8 accumulation around fifty fold indicating that maturation of the undifferentiated cell to a more macrophage-like cell facilitated IL-8 accumulation. Stimulating human alveolar macrophages with high concentrations of SEA caused an increase in IL-1 accumulation. However, when the cells were incubated with SEA in the presence of IL-1 receptor antagonist, there was no decrease in IL-8 accumulation. Addition of a neutralizing anti-IL-8 monoclonal antibody to the culture medium of SEA-stimulated macrophages significantly reduced the neutrophil chemotactic activity of the medium. These studies showed that IL-8 is a major neutrophil chemotaxin from human alveolar macrophages stimulated with SEA.
由于金黄色葡萄球菌是一种重要的人类病原体,且肺部感染以中性粒细胞浸润为特征,我们研究了葡萄球菌毒素肠毒素A(SEA)对人肺泡巨噬细胞合成和分泌白细胞介素-8(IL-8)的作用。随着SEA浓度的增加,巨噬细胞条件培养基中IL-8的积累增加。响应SEA浓度的增加,巨噬细胞中编码IL-8的mRNA浓度也升高。尽管单核细胞系U937能够对SEA作出反应并分泌IL-8,但在SEA刺激之前用佛波酯(PMA)处理可使IL-8的积累增加约五十倍,这表明未分化细胞成熟为更类似巨噬细胞的细胞促进了IL-8的积累。用高浓度SEA刺激人肺泡巨噬细胞会导致IL-1积累增加。然而,当细胞在存在IL-1受体拮抗剂的情况下与SEA一起孵育时,IL-8的积累没有减少。向SEA刺激的巨噬细胞培养基中添加中和性抗IL-8单克隆抗体可显著降低培养基的中性粒细胞趋化活性。这些研究表明,IL-8是SEA刺激的人肺泡巨噬细胞产生的主要中性粒细胞趋化因子。