Somatostatin Improved B Cells Mature in Macaques during Intestinal Ischemia-Reperfusion.

Ling Liu,Hao Wu,Qinghua Tan,Bin Hu,Rui Liu,Chengwei Tang,Chunhui Wang,Raul M Luque

doi:10.1371/journal.pone.0133692

Ling Liu, Hao Wu + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0133692

Copy DOI

Abstract

AimsIntestinal ischemia-reperfusion has been taken as an important pathophysiological process for multiple organ dysfunctions in critical patients. Recent studies reported that dual expression programs of the B cells receptors and Toll-like receptors on B-lymphocytes permit these ubiquitous cells to integrate both adaptive and innate immune functions. Our previous studies found that somatostatin inhibited the intestinal inflammatory injury after ischemia-reperfusion in macaques. However, the changes of B cells and the effects of somatostatin on B cells after intestinal ischemia-reperfusion were unclear.Methods15 macaques were divided into control, intestinal ischemia-reperfusion and somatostatin pretreatment groups. Immunohistochemistry was performed to identify the distributions of adaptive and innate immunity markers in the iliac mucosa. Hmy2.cir B lymphoblastoid cell line was cultured in vitro study. Enzyme-linked immunosorbent assay was used to measure IgM, IL-6 and SIgA, and the expressions of B cells transcription factors, PAX-5 and BLIMP-1, were detected by Western blotting.ResultsB2 lymphocytes in normal Peyer’s patches were presented the phenotype of PAX-5+CD20+CD5-. Ischemia-reperfusion increased the numbers and sizes of Peyer’s patches but with PAX-5+CD20-CD5- B cells, an unmatured set of B cells. Somatostatin partly kept the phenotype of mature B cells during ischemia-reperfusion. The innate immunity of B cells was inhibited whereas the adaptive immunity was increased in the intestinal mucosa in the somatostatin group, compared to the ischemia-reperfusion group. In vitro, somatostatin significantly inhibited IL-6 and promoted IgM by increasing the expression of both PAX-5 and BLIMP-1 in the proinflammatory condition.ConclusionIntestinal ischemia-reperfusion resulted in the proliferation of unmatured B cells which were involved in the augmentation of innate immunity. Somatostatin, with a bi-directional regulation function on innate as well as adaptive immunity of B cells, greatly improved B cells mature in macaques during ischemia-reperfusion. Preventive supplements of somatostatin may greatly limit intestinal injury and bacterial translocation during ischemia-reperfusion.

Highlights

Intestinal ischemia-reperfusion (IIR) is an important pathophysiological process in clinically critical illness, including severe trauma, shock, severe acute pancreatitis, infection, organ transplantation and other inflammatory-related diseases[1]
The innate immunity of B cells was inhibited whereas the adaptive immunity was increased in the intestinal mucosa in the somatostatin group, compared to the ischemia-reperfusion group
Intestinal ischemia-reperfusion resulted in the proliferation of unmatured B cells which were involved in the augmentation of innate immunity

Summary

Introduction

Intestinal ischemia-reperfusion (IIR) is an important pathophysiological process in clinically critical illness, including severe trauma, shock, severe acute pancreatitis, infection, organ transplantation and other inflammatory-related diseases[1]. Over the past two decades, clinical and basic studies have identified the gut as the "motor" of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) in these critical conditions [2,3,4]. It has been reported by our group and other groups, that exaggerated intestinal innate immune responses involving Toll-like receptor 4(TLR4) and proinflammatory cytokines contribute to massive intestinal and systemic inflammatory injury [5,6,7,8]. As basic and clinical research has evolved, the role of B cells in the mechanism of intestinal and systemic inflammatory injury after IIR remains unclear

Methods

Results

Conclusion