Role of innate immunity and altered intestinal motility in LPS- and MnCl2-induced intestinal intussusception in mice

Am J Physiol Gastrointest Liver Physiol. 2014 Mar 1;306(5):G445-53. doi: 10.1152/ajpgi.00264.2013. Epub 2014 Jan 9.


Intestinal intussusception (ISS) commonly causes intestinal obstruction in children. One mechanism that has been proposed to cause ISS is inflammation-induced alteration of intestinal motility. We investigated whether innate inflammatory factors or altered motility is required for induction of ISS by LPS. We compared rates of ISS among BALB/c and C57BL/6 mice, mice lacking lymphocytes or depleted of phagocytes, or mice with defects in the Toll-like receptor 4 (TLR4) signaling pathway following administration of LPS or the Ca(2+) analog MnCl2. At 6 or 2 h after administration of LPS or MnCl2, respectively, mice underwent image analysis to assess intestinal contraction rate or laparotomy to identify ISS. LPS-induced ISS (LPS-ISS) was observed in BALB/c mice, but not in C57BL/6 mice or any BALB/c mice with disruptions of TLR4 signaling. LPS-induced serum TNF-α, IL-6, and nitric oxide (NO) and intestinal NO levels were similar in BALB/c and C57BL/6 mice. The rate of LPS-ISS was significantly reduced in phagocyte-depleted, but not lymphocyte-deficient, mice. Intestinal contraction rates were reduced in LPS-ISS-susceptible BALB/c mice, but not in LPS-ISS-resistant C57BL/6 or TLR4 mutant mice, suggesting a role for reduced intestinal contraction rate in LPS-ISS susceptibility. This was tested with MnCl2, a Ca(2+) antagonist that reduced intestinal contraction rates and induced ISS, irrespective of mouse strain. Therefore, LPS-ISS is initiated by innate immune signaling that requires TLR4 and phagocytes but may be independent of TNF-α, IL-6, and NO levels. Furthermore, alteration of intestinal motility, specifically, reduced intestinal contraction rate, is a key factor in the development of ISS.

Keywords: inflammatory response; intestinal disorder; mouse model; pediatric.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chlorides / toxicity*
  • Female
  • Gastrointestinal Motility / drug effects*
  • Gene Expression Regulation / immunology
  • Immunity, Innate / drug effects
  • Immunity, Innate / physiology*
  • Intussusception / chemically induced*
  • Intussusception / immunology
  • Intussusception / metabolism
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / toxicity*
  • Male
  • Manganese Compounds
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism


  • Acute-Phase Proteins
  • Carrier Proteins
  • Chlorides
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Manganese Compounds
  • Membrane Glycoproteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • lipopolysaccharide-binding protein
  • manganese chloride