2. Academic Validation
  3. Causative role of mast cell and mast cell-regulatory function of disialyllacto-N-tetraose in necrotizing enterocolitis

Causative role of mast cell and mast cell-regulatory function of disialyllacto-N-tetraose in necrotizing enterocolitis

  • Int Immunopharmacol. 2021 Jul:96:107597. doi: 10.1016/j.intimp.2021.107597.
Wenting Zhang 1,  Jingqiu He-Yang 2,  Wenjun Zhuang 3,  Jie Liu 2,  Xiaoying Zhou 4
Affiliations

Affiliations

  • 1 School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu 213164, China; Affiliated Changzhou Children's Hospital of Nantong University, Changzhou, Jiangsu 213003, China.
  • 2 School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu 213164, China.
  • 3 Affiliated Changzhou Children's Hospital of Nantong University, Changzhou, Jiangsu 213003, China.
  • 4 School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu 213164, China. Electronic address: xiaoyingzhou@cczu.edu.cn.
PMID: 33812262 DOI: 10.1016/j.intimp.2021.107597
Abstract

Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates. Disialyllacto-N-tetraose (DSLNT), a function-unclear human milk-derived hexasaccharide, shows anti-NEC potential in previous animal studies. This study is aimed to explore the role of mast cell (MC), a fundamental cell type of mucosal immune system and protective DSLNT in regulating pathological process of NEC. For this purpose, infantile intestinal-tissues were collected from NEC neonates for examination of MCs and its proteases-positive cells. MC accumulation and MC-specific proteases (chymase, tryptase and Dipeptidyl Peptidase I) were firstly found in lesioned area of NEC infants in-vivo. Subsequent in-situ experiments on neonatal ileum segments showed that purified MC-chymase induced a destructive epithelial layer shedding from basement and microvascular endothelium damage in infantile intestinal segments. Human foreskin MC-activation model was established and DSLNT were applied; MC products (histamine and MC-proteases) were used as MC activation/degranulation indicators. In this in-vitro model, DSLNT pretreatment suppressed release of histamine, chymase and tryptase by MC to the tissue supernatants during lipopolysaccharide or complement C5a stimulation. Newborn rats were formula-hand-fed with or without DSLNT supplement and exposed to hypoxia/cold-stress to induce experimental-NEC-model. In NEC rats, DSLNT supplementation reduced the incidence and pathological scores of NEC, inhibited local accumulation of MC and reduced cytokines (IL-1β, IL-6 and TNF-α) levels in the ileum of rats. In conclusion, MC was causally implicated in epithelium barrier failure in pathogenesis of NEC. DSLNT favorably modulated MC homeostasis by regulating MC degranulation/accumulation, contributing to attenuated NEC. This indicated novel pathomechanisms and potential targets of NEC.

Keywords

Disialyllacto-N-tetraose; Human milk oligosaccharides; Mast cell; Necrotizing enterocolitis.

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