Peptidoglycan and lipoteichoic acid, components of the streptococcal cell wall, have marked and differential effects on adhesion molecule expression and the production of reactive oxygen species in human whole blood leukocytes

To elucidate the pathophysiology of infections with Streptococcus pyogenes we applied flow cytometric techniques to study dose-response and time-relat ed effects of the streptococcal cell-wall-derived components lipoteichoic a cid (LTA 0.005 to 50 mu g/ml) and peptidoglycan (10 and 100 mu g/ml) on the expression of leukocyte adhesion molecules, the CD14 receptor, and the pro duction of leukocyte reactive oxygen species (ROS). LTA (50 mu g/ml, 1-2 h) markedly increased the expression of CD11b (similar to 5-fold), CD11c (sim ilar to 2-fold) and CD11a. Concomitantly, CD62L was downregulated (60%). Pe ptidoglycan alone or in combination with LTA had little effect on adhesion molecules, except for an amplification of the downregulation of CD62L to 90 %. Monocyte CD14 expression was doubled by LTA. Leukocyte ROS production wa s 10-fold and 5-fold increased by peptidoglycan in granulocytes and monocyt es, respectively. LTA alone had no effect, while the combination of peptido glycan with LTA doubled the increase in ROS caused by peptidoglycan. Conclu sion: LTA and peptidoglycan had marked and differential effects: LTA caused mainly adhesion molecule modulation, whereas peptidoglycan mainly increase d ROS production. These changes are important in inflammatory cell activati on and recruitment, intracellular microbial killing and adverse tissue inju ry.