饮食微粒和钙在肠道巨噬细胞凋亡及白细胞介素-1β释放中的作用

The role of dietary microparticles and calcium in apoptosis and interleukin-1beta release of intestinal macrophages.

作者信息

Evans Stephen M, Ashwood Paul, Warley Alice, Berisha Fatmire, Thompson Richard P H, Powell Jonathan J

机构信息

Gastrointestinal Laboratory, Rayne Institute, St. Thomas' Hospital, London, England.

出版信息

Gastroenterology. 2002 Nov;123(5):1543-53. doi: 10.1053/gast.2002.36554.

DOI:10.1053/gast.2002.36554

PMID:12404229

Abstract

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-1beta and 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-1beta 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-1beta 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-1beta secretion, whereas blockade of phagocytosis inhibited calcium-induced apoptosis and interleukin-1beta release.

CONCLUSIONS

The endogenous luminal microparticle calcium phosphate Promotes apoptosis of intestinal macrophages. Concomitantly, interleukin-1beta 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.

摘要

背景与目的

肠道黏膜会接触到微米级的人造外源性颗粒（如二氧化钛）和新形成的内源性颗粒（磷酸钙）。有人提出这类微粒在炎症中发挥作用，在此我们研究了它们对固有层单核细胞的影响。

方法

从患有和未患有炎症性肠病的患者中分离出固有层单核细胞，并与脂多糖、二氧化钛、钙+/-柠檬酸盐以及脂多糖、钙和二氧化钛的结合物一起孵育。通过酶联免疫吸附测定法测量培养上清液中的白细胞介素-1β和白细胞介素-1受体拮抗剂，并通过流式细胞术检测巨噬细胞凋亡。在正常外周血单核细胞中进行机制研究。

结果

炎症性肠病中白细胞介素-1β的基线水平和巨噬细胞凋亡高于正常固有层单核细胞。脂多糖和二氧化钛没有额外影响，但钙，尤其是结合物，会根据炎症程度诱导白细胞介素-1β释放。用于防止原位形成磷酸钙的柠檬酸盐可消除固有层单核细胞的刺激。钙和结合物也会增加巨噬细胞凋亡。在外周血单核细胞中，抑制半胱天冬酶1可减少白细胞介素-1β分泌，而阻断吞噬作用可抑制钙诱导的凋亡和白细胞介素-1β释放。