PAF and CD18 mediate neutrophil infiltration in upper gastrointestinal tract during intra-abdominal sepsis

被引:17
作者
Beyer, AJ
Smalley, DM
Shyr, YM
Wood, JG
Cheung, LY [1 ]
机构
[1] Univ Kansas, Med Ctr, Dept Surg, Kansas City, KS 66160 USA
[2] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA
[3] Natl Yang Ming Univ, Vet Gen Hosp, Dept Surg, Taipei 11217, Taiwan
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 275卷 / 03期
关键词
cecal ligation and incision; intercellular adhesion molecule 1; leukocyte adhesion; WEB-2086;
D O I
10.1152/ajpgi.1998.275.3.G467
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Neutrophil infiltration is a critical event in the development of multiple organ failure during sepsis. We hypothesized that platelet-activating factor (PAF) release contributes to neutrophil infiltration in the gastrointestinal tract during sepsis. In the first experiments we administered exogenous PAF (1.56, 6.25, 25, and 100 ng.kg(-1).min(-1) for 30 min) to urethan-anesthetized Sprague-Dawley rats. PAF was administered alone or in combination with either the PAF antagonist WEB-2086 (250 mu g.kg(-1).min(-1)), a monoclonal antibody (MAb) to CD18, or a MAb to intercellular adhesion molecule 1 (ICAM-1). In separate groups of rats, cecal ligation and incision (CLI) was performed to create intra-abdominal sepsis, which we hypothesized would stimulate the release of endogenous PAF. CLI was performed in rats given either saline, WEB-2086, anti-CD18, or anti-ICAM-1 MAb. After these experiments, tissue myeloperoxidase (MPO) levels were determined as a marker of neutrophil infiltration. Both exogenous PAF and CLI induced significant increases in MPO activity in the stomach and duodenum. These increases were significantly attenuated by WEB-2086, anti-CD18 MAb, and anti-ICAM-1 MAb in both PAF- and CLI-treated rats. These results suggest that both the inflammatory mediator PAF and the CD18 integrins play a major role in neutrophil infiltration in the upper gastrointestinal tract during sepsis.
引用
收藏
页码:G467 / G472
页数:6
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