title: Role of innate immunity and altered intestinal motility in LPS- and MnCl2-induced intestinal intussusception in mice.
abstract: 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.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas;
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Killoran
authors.forename: Amber D
authors.initials: AD
authors.lastname: Miller
authors.forename: Karen S
authors.initials: KS
authors.lastname: Uray
authors.forename: Norman W
authors.initials: NW
authors.lastname: Weisbrodt
authors.forename: Robia G
authors.initials: RG
authors.lastname: Pautler
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Goyert
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Conner
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D007443:Intussusception / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D017895:Manganese Compounds; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D002712:Chlorides; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017895:Manganese Compounds; D008562:Membrane Glycoproteins; D051197:Toll-Like Receptor 4; D000099231:Lipopolysaccharide-Binding Protein; C493487:Tlr4 protein, mouse; C025340:manganese chloride
keywords: inflammatory response; intestinal disorder; mouse model; pediatric