MONOCYTE MACROPHAGES EVOKE EPITHELIAL DYSFUNCTION - INDIRECT ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA/

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 .