Monocyte/macrophages evoke epithelial dysfunction: indirect role of tumor necrosis factor-alpha.
We examined the ability of monocytes (MPhi) activated by bacterial products to alter epithelial physiology. Confluent monolayers of the T84 colonic epithelial cell line were grown on filter supports and then cocultured in the presence of human MPhi with or without the activating agents bacterial lipopolysaccharide and the bacterial tripeptide formyl-methionyl-leucyl-phenylalanine. After 24 or 48 h, monolayers were mounted in Ussing chambers where parameters of epithelial function were measured. Exposure to activated MPhi resulted in a significant increase (P < 0.05) in baseline short-circuit current (250% after 48 h) that was associated with enhanced secretion of Cl-. In addition, epithelial permeability was significantly increased as shown by reduced transepithelial resistance and increased flux of 51Cr-EDTA. Activated MPhi produced substantial amounts (approximately 3 ng/ml at 48 h) of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha was identified as a key mediator acting via an autocrine mechanism to induce epithelial pathophysiology. Our data show that MPhi, when activated by common bacterial components, are potent effector cells capable of initiating significant changes in the transport and barrier properties of a model epithelium.
Zareie
M
M
Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
McKay
D M
DM
Kovarik
G G
GG
Perdue
M H
MH
D000328:Adult; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D003106:Colon; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012475:Salmonella; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D009240:N-Formylmethionine Leucyl-Phenylalanine