HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/R1839    most recent 00412.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tillinger, W. Articles by Barrett, K. E. Search for Related Content PubMed PubMed Citation Articles by Tillinger, W. Articles by Barrett, K. E.

INFLAMMATION, CYTOKINES, NEUROIMMUNE INTERACTIONS

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

¹Division of Gastroenterology, Department of Medicine and ³Department of Pathology, University of California, San Diego, School of Medicine, La Jolla, California; and ⁴Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and ²Department of Medicine, Hartmann Hospital, Vienna, Austria

Submitted 11 June 2007 ; accepted in final form 28 September 2008

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.

neutrophil activation; inflammatory bowel disease; hypertonic saline solution; inflammation; epithelium