Am. J. Respir. Cell Mol. Biol., Vol 10, No. 3, Mar 1994, 284-289.
Heat-killed pneumococci and pneumococcal capsular polysaccharides stimulate tumor necrosis factor-alpha production by murine macrophages
SQ Simpson, R Singh and DE Bice
Department of Medicine, University of New Mexico, Albuquerque 87131- 5271.
Tumor necrosis factor-alpha (TNF) is an important humoral mediator of
sepsis and endotoxin-induced shock. However, Streptococcus pneumoniae, a
gram-positive organism, is the most common causative agent of
community-acquired pneumonia and sepsis. We hypothesized that the
pathogenesis of pneumococcal pneumonia and sepsis involves pneumococcus-
stimulated TNF synthesis, and we tested that hypothesis in vitro by
comparing heat-killed type III and type V pneumococcus and 23-valent
purified pneumococcal capsular polysaccharides with Escherichia coli and
purified lipopolysaccharide (LPS) as stimuli for TNF production by the
murine macrophage cell line RAW 264.7. We evaluated TNF production in
response to various doses and times of exposure to these agents, as well as
the effects of indomethacin on TNF production in response to these agents.
Stimulation with both types of heat-killed pneumococcus resulted in TNF
production in a dose-response fashion, as did stimulation with E. coli.
Fewer type III pneumococci (10 bacteria/ml) were required to stimulate
significant TNF secretion than either type V pneumococcus or E. coli, but
the overall dose-response curves of the three bacteria were similar. The
dose-response curves for pneumococcal capsular polysaccharides and LPS were
very similar, although at the highest concentration pneumococcal capsular
polysaccharides stimulated more TNF secretion than did LPS (469 versus 213
U/ml). The kinetics of pneumococcus-stimulated TNF secretion were identical
to the kinetics of LPS-stimulated TNF secretion. In the presence of
indomethacin, pneumococcus-stimulated TNF production decreased by 87.5%, as
compared with pneumococcus alone. In contrast, LPS with indomethacin
stimulated 19.5% more TNF than LPS alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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Copyright © 1994 American Thoracic Society.
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