Postoperative ileus is the delay in normal gastrointestinal motility that frequently occurs after intestinal surgery. This condition depends on the activation of macrophages and dendritic cells. The molecular chain of events linking to the role of dendritic cells involves the production of proinflammatory cytokines by dendritic cells, stimulation of memory T cells to produce interferon, and the subsequent activation of macrophages (and monocytes) to express nitric oxide synthase. The nitric oxide that is produced is responsible for the intestinal muscle paralysis associated with postoperative ileus. The mechanisms involved in the initiation and progression of this process are not fully understood. Therefore, a group of scientists conducted a study to explore how the dendritic cells are activated and the role of the microbiota in the development of postoperative ileus.
An intestinal manipulation technique was used to induce postoperative ileus in laboratory mice lacking Irf4-dependent cD103+cD11b+ dendritic cells (a dendritic cell subset that is unique to the intestine) and in mice with a normal dendritic cell population. The severity of postoperative ileus was tested determining the time to secrete an intestinally inserted small glass ball in a group of mice, and by orally dosing another group with a dye to examine its intestinal distribution after the mice were euthanized. It was noted that the severity of postoperative ileus was reduced with the absence of cD103+cD11b+ dendritic cells, indicating their importance for the development of the disease.
The involvement of microbiota in the activation of intestinal dendritic cells and development of postoperative ileus was determined by administering antibiotics to the study mice to diminish the microbiota population. Analysis using ELISA and RT-PCR showed significant reduction of IL-12 and nitric oxide synthase indicating that dendritic cell activation is microbiota dependent. There was also a considerable decrease in interferon suggesting a blocking of T helper cell activity. In addition to the molecular findings, postoperative ileus was also reduced due to depletion of the microbiota.
The study results show that a specialized set of dendritic cells found in the intestine play an important role in the regulation of intestinal motility and the development of postoperative ileus. Also, intestinal microbiota are necessary for dendritic cell, monocyte, and macrophage responses in postoperative ileus. Altering the microbiota may serve as preventive measure against dendritic cells activation and the development of postoperative ileus.
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