PNEUMOCOCCAL CELL-WALL ACTIVATES NF-KAPPA-B IN HUMAN MONOCYTES - ASPECTS DISTINCT FROM ENDOTOXIN

The transcription factor NF-kappa B plays a central role in inflammati on by controlling the transcription of multiple genes which participat e in the acute phase response. Mice with a targetted disruption of the p50 subunit of NF-kappa B are hyper-susceptible to challenge with pne umococci but not endotoxin. We sought to clarify the role of NF-kappa B in the host response to the critical inflammatory component of pneum ococci, the cell wall. Activation of NF-kappa B was monitored by expre ssion of luciferase from cells transfected with an NF-kappa B dependen t luciferase reporter construct. 70Z/3 murine pre-B cells and U937 hum an monocytes failed to produce luciferase in response to 10(7) pneumoc occic 10 mu g cell wall; strong responses were obtained with 10 mu g o f LPS. In contrast, THP-1 human monocytes showed strong luciferase pro duction with all three stimuli: LPS, intact pneumococci and cell wall. The response was time and dose dependent. Cell wall activity was reta ined despite alteration of the choline of the teichoic acid or proteas e treatment suggesting the glycopeptide backbone to be a critical dete rminant of bioactivity. We conclude that activation of NF-kappa B by p neumococci is restricted to certain cells and that this proinflammator y activity may be a specific feature of the pneumococcal cell wall gly copeptide backbone. (C) 1996 Academic Press Limited