Monocyte/macrophage activation by normal bacteria and bacterial products -Implications for altered epithelial function in Crohn's disease

Intestinal immune cells are less reactive than those in the peripheral bloo d; however, such cells from patients with Crohn's disease may be more respo nsive to bacterial products. Our study examined if nonpathogenic bacteria o r lipopolysaccharide (LPS), can affect epithelial function in the presence of monocytes/macrophages. Lamina propria mononuclear cells (LPMCs) and peri pheral blood monocytes (PBMs) were obtained from patients with Crohn's dise ase and control patients, Filter-grown T84 epithelial monolayers were co-cu ltured with nonactivated or LPS-activated LPMCs or PBMs for 48 hours. Epith elial secretory [baseline short-circuit current (Isc) and Delta Isc to fors kolin] and barrier (transepithelial electrical resistance) parameters were measured in Ussing chambers. LPS-activated PBMs from both controls and pati ents with Crohn's disease significantly increased Isc (similar to 300%) and reduced transepithelial electrical resistance (similar to 40%). Epithelial function was not altered after co-culture with control LPMCs +/- LPS, Howe ver, LPMCs from patients with Crohn's disease spontaneously secreted tumor necrosis factor-cy, and induced epithelial changes similar to those produce d by LPS-activated PBMs, Go-culture with control Escherichia coli and PBMs induced comparable changes in epithelial physiology, which were abrogated b y anti-tumor necrosis factor-alpha antibody, Vile conclude that LPMCs of pa tients with Crohn's disease are spontaneously activated, possibly by gram-n egative luminal bacteria, and can directly cause significant alterations in epithelial ion transport and barrier functions.