INTERLEUKIN-8 (IL-8) IS A MAJOR NEUTROPHIL CHEMOTAXIN FROM HUMAN ALVEOLAR MACROPHAGES STIMULATED WITH STAPHYLOCOCCAL-ENTEROTOXIN-A (SEA)

Since Staphylococcus aureus is an important human pathogen, and infect ion of the lungs is characterized by neutrophil infiltration we studie d the role of a staphylococcal toxin, enterotoxin A (SEA) on the synth esis and secretion of IL-8 by human alveolar macrophages. As SEA conce ntration was increased, the IL-8 accumulation in the macrophage condit ioned medium increased. The concentration of mRNA encoding IL-8 was al so elevated in the macrophage in response to increases in SEA concentr ation. Although the monocytic cell line U937 was able to respond to SE A and secrete IL-8, treatment with PMA prior to SEA stimulation increa sed the IL-8 accumulation around fifty fold indicating that maturation of the undifferentiated cell to a more macrophage-like cell facilitat ed IL-8 accumulation. Stimulating human alveolar macrophages with high concentrations of SEA caused an increase in IL-1 accumulation. Howeve r, when the cells tt-ere incubated with SEA in the presence of IL-1 re ceptor antagonist, there was no decrease in IL-8 accumulation. Additio n of a neutralizing anti-IL-8 monoclonal antibody to the culture mediu m of SEA-stimulated macrophages significantly reduced the neutrophil c hemotactic activity of the medium. These studies showed that IL-8 is a major neutrophil chemotaxin from human alveolar macrophages stimulate d with SEA.