AJP - Gastrointestinal and Liver Physiology, Vol 267, Issue 2 213-G219, Copyright © 1994 by American Physiological Society
Differential production of TNF by Kupffer cells after phagocytosis of E. coli and C. albicans
J. K. Olynyk, G. M. Matuschak, A. J. Lechner, R. S. Britton, T. L. Tredway, R. O'Neill and B. R. Bacon
Division of Gastroenterology, Saint Louis University Health Sciences Center, Missouri.
Tumor necrosis factor (TNF) of hepatic origin is thought to play a pivotal
role early in the genesis of the septic shock syndrome, regardless of
microbial etiology. To determine if production of TNF by Kupffer cells
varies with microbial taxonomic class, we measured TNF secretory responses
in primary cultures of rat Kupffer cells to numerically equivalent
gram-negative bacterial or fungal phagocytic challenges. After a 30-min
exposure to media, latex beads, soluble Escherichia coli lipopolysaccharide
(LPS; serotype 055:B5), live or Formalin-fixed E. coli (serotype 055:B5),
live or Formalin-fixed yeast-phase Candida albicans, or live hyphal-phase
Candida, samples of culture supernatant were assessed at 30, 60, 120, and
240 min and at 24 h for TNF bioactivity by L929 cell cytotoxicity. Compared
with media and latex bead controls, TNF levels progressively increased for
up to 240 min after either LPS and equivalently in live E. coli or
Formalin-fixed E. coli groups (P < 0.05). Formalin-fixed yeast-phase and
live extracellular hyphal-phase C. albicans failed to stimulate production
of TNF at any time point (6.9 +/- 0.7 and 8.7 +/- 0.4 U/ml, respectively,
at t = 240 min; P < 0.05 vs. E. coli). In contrast, internalization of
live yeast-phase C. albicans with subsequent hyphal formation and growth
within Kupffer cells was accompanied by a rise in supernatant TNF levels
(14.5 +/- 1.8 U/ml at t = 240 min).(ABSTRACT TRUNCATED AT 250 WORDS)
