Tillinger Wolfgang, McCole Declan F, Keely Stephen J, Bertelsen Lone S, Wolf Paul L, Junger Wolfgang G, Barrett Kim E
Division of Gastroenterology, Department of Medicine, University of California, San Diego, Mailcode 0063, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R1839-45. doi: 10.1152/ajpregu.00412.2007. Epub 2008 Oct 1.
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.
多形核中性粒细胞（PMN）的跨上皮迁移在肠道炎症性疾病（如炎症性肠病）中起着关键作用。高渗盐水（HS）对PMN功能具有多种抑制作用。我们推测HS可以抑制PMN的跨上皮迁移，从而预防实验性结肠炎中的炎症事件。将分离的人PMN用HS（40 mM）处理，并用N-甲酰甲硫氨酰亮氨酰苯丙氨酸诱导其穿过T84上皮细胞单层的迁移。通过监测Ussing室中跨上皮电导的变化来评估单层破坏情况。通过口服给予葡聚糖硫酸钠（DSS）诱导小鼠结肠炎。动物每天两次腹腔注射4或8 ml/kg的7.5%盐水，持续7天。对照组接受等量的生理盐水（NS，n = 6）或不进行腹腔内治疗（DSS，n = 12）。根据疾病活动指数和组织学评分评估炎症的严重程度。与未处理的对照细胞相比，体外HS处理PMN显著降低了细胞迁移和T84单层的破坏（n = 5，P < 0.05）。HS的这种作用具有剂量依赖性。体内HS治疗也减少了结肠炎诱导的肠道组织损伤，与NS和DSS组相比，组织学评分有所改善表明了这一点。我们得出结论，HS在体外抑制PMN的跨上皮迁移，在体内抑制小鼠结肠炎模型中的肠道组织损伤。因此，HS可能具有减少PMN介导的肠道损伤的临床价值。
