Hypertonic saline reduces neutrophil-epithelial interactions in vitro and gut tissue damage in a mouse model of colitis

Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R1839-45. doi: 10.1152/ajpregu.00412.2007. Epub 2008 Oct 1.

Abstract

Transepithelial migration of polymorphonuclear neutrophils (PMN) plays a crucial role in inflammatory conditions of the intestine, such as inflammatory bowel diseases. Hypertonic saline (HS) exerts various inhibitory effects on PMN function. We hypothesized that HS could inhibit transepithelial migration of PMN and thereby prevent inflammatory events in experimental colitis. Isolated human PMN were treated with HS (40 mM), and their transmigration across a monolayer of T84 epithelial cells was induced by N-formyl-methionyl-leucyl-phenylalanine. Monolayer disruption was assessed by monitoring changes in transepithelial conductance in an Ussing chamber. Colitis in mice was induced by oral administration of dextran sulfate sodium (DSS). Animals were treated with 4 or 8 ml/kg of 7.5% saline intraperitoneally two times daily for 7 days. Controls received equivalent volumes of normal saline (NS, n = 6) or no intraperitoneal treatment (DSS, n = 12). The severity of inflammation was evaluated based on disease activity index and histology score. HS treatment of PMN in vitro significantly reduced cell migration and the disruption of T84 monolayers compared with untreated control cells (n = 5, P < 0.05). This effect of HS was dose dependent. HS treatment in vivo also reduced colitis-induced gut tissue damage, as indicated by an improved histology score compared with the NS and DSS groups. We conclude that HS inhibits transepithelial migration of PMN in vitro and gut tissue damage in vivo in a mouse model of colitis. Thus HS may have clinical value to reduce PMN-mediated intestinal damage.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • CD11b Antigen / metabolism
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / pathology
  • Colitis / prevention & control*
  • Dextran Sulfate
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • Humans
  • Injections, Intraperitoneal
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Permeability
  • Saline Solution, Hypertonic / administration & dosage
  • Saline Solution, Hypertonic / pharmacology*
  • Severity of Illness Index
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • CD11b Antigen
  • ITGAM protein, human
  • Saline Solution, Hypertonic
  • Dextran Sulfate