DIFFERENTIATION-ASSOCIATED ANTIMICROBIAL FUNCTIONS IN HUMAN COLON ADENOCARCINOMA CELL-LINES

We report that the enterocytic cells of the HT-29 glc(-/+) cell subpop ulation strongly expressed two antimicrobial enzymes: the lysozyme add alpha(1)-antitrypsin. Moreover, we found that 20 to 30% of these cell s expressed positive immunoreactivity using the mAbs directed against the gut porcine PR-39 and cecropin P1 antimicrobial peptides, but did not express immunreactivity against the human antimicrobial polymorpho nucleated neutrophil-associated HNP 1-3 defensin and the Xenopus skin magainin. The HT-29 glc(-/+) cell subpopulation develops bacteriolytic activity against the enterovirulent diffusely adhering C1845 Escheric hia coli characterized by dramatic alterations of the bacterial cell, suggesting lysis, and bacterial death. In contrast, no expression of i mmunoreactivity against the antimicrobial peptides and no C1845 bacter ial alteration were found in the cultured human embryonic undifferenti ated INT407 cells and the colon adenocarcinoma T-S4 crypt cells. The d evelopment of the bacterial alteration and the expression of the antim icrobial components were examined as a function of the cell differenti ation using the Caco-X cell line which spontaneously differentiates in culture. We found that the bacterial alteration and the expression of the PR-39 immunoreactivity are differentiation-associated events. Alt ogether, our results suggest that in the intestine the enterocytes cou ld develop antimicrobial defenses participating in the protection of t he gut epithelium against enterovirulent microorganisms. (C) 1996 Acad emic Press, Inc.