LIPOTEICHOIC ACID INDUCES SECRETION OF INTERLEUKIN-8 FROM HUMAN BLOODMONOCYTES - A CELLULAR AND MOLECULAR ANALYSIS

Invasion by gram-positive and gram-negative bacterial organisms is cha racterized immunopathologically by the activation of mononuclear phago cytic cells, leading to the elaboration of macrophage-derived regulato ry and chemotactic factors, and the resultant influx of inflammatory l eukocytes. Little is known regarding the mechanisms by which gram-posi tive organisms initiate macrophage activation and subsequent inflammat ion. In this investigation, we postulated that lipoteichoic acid (LTA) purified from two different gram-positive bacterial species was an im portant signal for the expression of chemotactic cytokines from human peripheral blood monocytes (PBM). In initial experiments, we demonstra ted that cell-associated interleukin-8 (IL-8) was expressed by mononuc lear phagocytes present in inflamed areas of endocardium in cases of a cute Staphylococcus aureus endocarditis. We next demonstrated that LTA purified from either Staphylococcus aureus or Streptococcus pyogenes induced the time- and dose-dependent expression of IL-8 mRNA and prote in from human PBM. The expression of IL-8 mRNA from LTA- but not lipop olysaccharide (LPS)-treated PBM was superinduced by concomitant treatm ent with cycloheximide, indicating that the expression of IL-8 mRNA fr om LTA-treated PBM was negatively controlled by repressor proteins. Fu rthermore, mRNA stability studies indicated that IL-8 mRNA was less st able in the presence of LTA than in the presence of LPS. Our findings indicate that LTA can induce the secretion of the polymorphonuclear le ukocyte chemotactic factor IL-8 and that LTA may be an important cellu lar mediator of inflammatory cell recruitment that characterizes immun e responses to gram-positive bacterial infections.