Fatty diets retarded the propulsive function of and attenuated motility in the gastrointestinal tract of rats.

Digestive functions are considered to be alterable by the ingestion of fatty diets. This study aimed to investigate the hypothesis that dietary fats may exert site-specific effects on the propulsive functions of the gastrointestinal (GI) tract. After male Wistar rats were fed either low-fat diet or high-fat diet (HFD) for 8 weeks, the propulsive function of the luminal contents of the entire GI tract was simultaneously examined in vivo. In comparison with a low-fat diet, an HFD significantly increased the body weight gains but significantly decreased the diet and caloric intakes, fecal weights, and fecal pellet numbers. Gastric emptying in the HFD-fed rats tended to be delayed, but this was not significant. High-fat diet feeding significantly slowed the small bowel transit times, and the luminal residuals emptied from the gastric antrum were largely accumulated in the proximal parts of the small intestine. An HFD also significantly prolonged the colonic transit times. In conclusion, fatty diets retarded the propulsive function of the entire GI tract, and the delayed gastroduodenal transit of fatty diets may act as a primary causal factor for producing the attenuated motile function of the GI tract in rats.

Membrane-bound proteinase 3 and PAR2 mediate phagocytosis of non-opsonized bacteria in human neutrophils.

The molecular mechanisms underlying the non-opsonic phagocytosis of bacteria by neutrophils are poorly understood. We previously reported the efficient uptake of Streptococcus sanguinis by human neutrophils in the absence of opsonins. To characterize the phagocytosis receptor, protein lysates from neutrophils and HL-60 cells were subjected to affinity chromatography using epoxy beads coated with S. sanguinis. Denaturing electrophoresis of the eluted proteins and subsequent mass spectrometry revealed that one of the proteins eluted from neutrophils was proteinase 3 (PR3). Enzymatic cleavage of the glycosylphosphatidylinositol linker of NB1, a co-receptor for membrane-bound PR3 (mPR3), significantly reduced the phagocytosis of S. sanguinis. In addition, the neutralization of mPR3 with antibody reduced both binding and phagocytosis of S. sanguinis. Treatment of neutrophils with a serine proteinase inhibitor indicated that protease activity is required for phagocytosis. Thus, we studied whether protease-activated receptor 2 (PAR2) is involved in signal transmission from mPR3 during this process. Indeed, neutralizing antibodies against PAR2 inhibited phagocytosis and S. sanguinis-induced calcium mobilization desensitized PAR2. Furthermore, the phagocytosis of S. sanguinis and the concomitant activation of Rho family GTPases were inhibited by the intracellular calcium chelator, BAPTA-AM. Collectively, mPR3 acts as a non-opsonic phagocytosis receptor for bacteria probably by activating PAR2 in neutrophils.