Intracellular activation of complement C3 in Paneth cells improves repair of intestinal epithelia during acute injury

Immunotherapy. 2018 Nov;10(15):1325-1336. doi: 10.2217/imt-2018-0122. Epub 2018 Nov 1.

Abstract

Aim: To explore whether Paneth cells (PCs) and complement system collaborate in the repair of enteric epithelia during acute gastrointestinal injury (AGI).

Methods: Wild-type C57BL/6 mice were employed to induce AGI by performing colon ascendens stent surgery, with sham-operated as control. Exogenous C3 treatment was applied at 6-h postsurgery. After 48 h, overall survival, intestinal damage severity, and C3 intracellular activation were assessed in both epithelial cells and PCs.

Results: AGI caused a high mortality, while C3 therapy significantly attenuated epithelial damages and improved survival. Besides, exogenous C3 in vitro enhanced the proliferation and activity of PCs. Importantly, intracellular C3 activation was observed inside of PCs under C3 co-stimulation in vitro.

Conclusion: C3 immunotherapy might play a valuable role in turnover of gut epithelia through intracellular activation in PCs.

Keywords: Paneth cells; abdominal infection; complement C3; gut epithelia; immunotherapy; intestinal injury; intracellular activation; lysozyme; repair and regeneration; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Colon / surgery
  • Complement Activation
  • Complement C3 / therapeutic use*
  • Disease Models, Animal
  • Female
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / therapy*
  • Humans
  • Immunotherapy / methods*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / physiology
  • Intracellular Space
  • Mice
  • Mice, Inbred C57BL
  • Paneth Cells / drug effects*
  • Paneth Cells / physiology
  • Wound Healing

Substances

  • Complement C3