Biological roles of somatostatin in intestinal macaque Peyer's patch B cells

Abstract

To explore the effects of somatostatin (SST) on macaque intestinal Peyer's patches (PP) in immune B cells and explore its mechanism. A total of 15 healthy adult macaques were randomized into control,MODS and MODS+SST groups.Surgical procedures of MODS in macaques: For MODS group, anesthesia was maintained with diazepam (0.16 ± 0.09) mg×kg(-1)×h(-1), i.v.). A catheter was inserted into a peripheral vein for infusing 0.9% saline and 20 g glucose (0.1-0.2 ml×kg(-1)×min(-1), i.v.gtt) for 24 h. Midline laparotomy was performed. Then superior mesenteric artery (SMA) was isolated and occluded with a microsurgical clip. After a 1-hour occlusion, clip was removed and intestinal perfusion reestablished.In MODS+SST group, SST was infused intravenously with a syringe pump at a dosage of 5 µg×kg(-1)×h(-1) for 5 min before an occlusion of SMA until the end of experiment.Venous blood samples were redrawn and the animals sacrificed at 24 h post-IIR for harvesting vital organs. The changes of organs and the morphological changes of PP were detected by hematoxylin and eosin. And the expressions of TLR4, TLR2, CD20, CD5, α4β7 and MadCAM-1 were evaluated by immunohistochemical staining.Semiquantitative immunohistochemical analysis of raw data was performed with Image Pro Plus 4.0 software. All animals in MODS group presented with small intestines PP increased both in number and size compared with control group (4.8 ± 2.3 vs 1.2 ± 0.9, P < 0.05). After prophylactic to SST, compared with MODS group, the number of PP in small intestines in MODS+SST group decreased (2.7 ± 1.5 vs 4.8 ± 2.3, P < 0.05), but there was no significant difference in morphological of PP. The expression of CD20(+) of B-cells in MODS group was significantly lower than in normal group (integrated optical density (IOD), 64.22 ± 42.45 vs 100.00 ± 86.67, P < 0.05).Interestingly, after prophylactic dosing of SST, the expression level of CD20(+) of B-cells elevated significantly in MODS+SST group compared with that in MODS group (129.02 ± 75.04 vs 64.22 ± 42.45, P < 0.05). There was no α4β7 expression of B-cells in PP of macaques in three groups. And the expression level of MadCAM-1 was strongly up-regulated after prophylactic dosing of STT compared with MODS. After prophylactic dosing of STT, the expressions of TLR4 and TLR2 declined significantly compared with MODS (56.60 ± 6.83 vs 93.26 ± 10.40, 35.56 ± 4.71 vs 62.06 ± 9.90, P < 0.05). Plasma cells within normal intestinal mucosa were predominantly located in lamina propria. During MODS, plasma cells almost disappeared. After prophylactic dosing of STT, compared to MODS group, there was a rebound of plasma cells. Endogenous SST controls the switch of B-cells in PP between natural and acquired immunities. The prophylactic dosing of SST could convert excessive natural immunity into beneficial acquired humoral immunity. And SST may facilitate the prevention of multiple organ dysfunction syndromes.