Background & Aims: The intestinal mucosa is exposed to micron-sized, man-made exogenous particles (e.g., titanium dioxide) and freshly formed endogenous particles (calcium phosphate). A role for such microparticles in inflammation has been proposed, and here we examined their effects on lamina propria mononuclear cells. Methods: Lamina propria mononuclear cells were isolated from patients with and without inflammatory bowel disease and incubated with lipopolysaccharide, titanium dioxide, and calcium ± citrate, as well as a conjugate of lipopolysaccharide, calcium, and titanium dioxide. Interleukin-1β interleukin-1 receptor antagonist were measured by enzyme-linked immunosorbent assay in culture supernatants and macrophage apoptosis by flow cytometry. Mechanistic studies were undertaken in normal peripheral blood mononuclear cells. Results: Baseline levels of interleukin-1β and macrophage apoptosis were greater in inflammatory bowel disease than in normal lamina propria mononuclear cells. Lipopolysaccharide and titanium dioxide had no additional effect, but calcium, and more so the conjugate, induced interleukin-1β release in proportion to the degree of inflammation. Citrate, used to prevent in situ calcium phosphate formation, negated lamina propria mononuclear cell stimulation. Macrophage apoptosis was also increased by calcium and the conjugate. In peripheral blood mononuclear cells, inhibition of caspase 1 reduced interleukin-1β secretion, whereas blockade of phagocytosis inhibited calcium-induced apoptosis and interleukin-1β release. Conclusions: The endogenous luminal microparticle calcium phosphate Promotes apoptosis of intestinal macrophages. Concomitantly, interleukin-1β is released, which is enhanced in the presence of inflamed cells and/or exogenous dietary microparticles. Endogenous or exogenous microparticles could aggravate the ongoing inflammation of inflammatory bowel disease.
|Original language||English (US)|
|Number of pages||11|
|State||Published - Nov 1 2002|
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