INTERNALIZATION OF STAPHYLOCOCCUS-AUREUS BY ENDOTHELIAL-CELLS INDUCESCYTOKINE GENE-EXPRESSION

The ability of the vascular endothelium to elaborate cytokines in resp onse to gram-positive sepsis has received limited attention. This stud y examined cytokine expression by human umbilical vein endothelial cel ls (EC) following infection with a gram-positive bacterial pathogen, S taphylococcus aureus. S. aureus infection of EC resulted in the produc tion of interleukin-6 (IL-6) and IL-1 beta. For IL-6, message was dete cted at 3 h after infection, protein was present at 24 h, and both mes sage and protein persisted for 72 h, IL-1 beta message was detected at 12 h, IL-1 beta protein was detected at 24 h, and both persisted for 72 h. Message for colony-stimulating factor 1 remained unaltered. UV-k illed S. aureus also elicited IL-1 beta and IL-6 message and protein e xpression at 24 and 48 h. Twenty-one clinical isolates of S. aureus we re tested, and all induced IL-6 release by 48 h, However, the laborato ry strain 8325-4 did not induce cytokine expression at any time point and was internalized by EC 1,000-fold less than other strains were, in ternalization of latex beads by EC did not induce IL-6 gene expression . Furthermore, cytochalasin D treatment of the EC prevented IL-1 and I L-6 induction by S. aureus but not by tumor necrosis factor alpha or l ipopolysaccharide. These results indicate that S. aureus is a potent i nducer of IL-1 and IL-6 in EC and that internalization of S. aureus by EC is necessary for their cytokine expression. Thus, our data suggest that the vascular endothelium may play an important role in the patho genesis of septicemia caused by gram-positive organisms.