M. Zareie et al., MONOCYTE MACROPHAGES EVOKE EPITHELIAL DYSFUNCTION - INDIRECT ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA/, American journal of physiology. Cell physiology, 44(4), 1998, pp. 932-939
We examined the ability of monocytes (M Phi) activated by bacterial pr
oducts to alter epithelial physiology. Confluent monolayers of the T84
colonic epithelial cell line were grown on filter supports and then c
ocultured in the presence of human M Phi with or without the activatin
g agents bacterial lipopolysaccharide and the bacterial tripeptide for
myl-methionyl-leucylphenylalanine. After 24 or 48 h, monolayers were m
ounted in Ussing chambers where parameters of epithelial function were
measured. Exposure to activated M Phi resulted in a significant incre
ase (P < 0.05) in baseline short-circuit current (250% after 48 h) tha
t was associated with enhanced secretion of Cl-. In addition, epitheli
al permeability was significantly increased as shown by reduced transe
pithelial resistance and increased flux of Cr-51-EDTA. Activated M Phi
produced substantial amounts (similar to 3 ng/ml at 48 h) of tumor ne
crosis factor-alpha (TNF-alpha). TNF-alpha was identified as a key med
iator acting via an autocrine mechanism to induce epithelial pathophys
iology. Our data show that M Phi, when activated by common bacterial c
omponents, are potent effector cells capable of initiating significant
changes in the transport and barrier properties of a model epithelium
.