Neutrophil-dependent oxidative stress in ulcerative colitis

Abstract

Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity and epithelial injury in ulcerative colitis (UC). Current advances have defined the mechanisms by which neutrophils are activated or migrate across mucosal epithelia. A better understanding of this process will likely provide new insights into novel treatment strategies for UC. Especially, activated neutrophils produce reactive oxygen and nitrogen species within intestinal mucosa, which induce oxidative stress. In clinically, we have succeeded to develop a novel granulocytes adsorptive apheresis therapy for UC. In this article, we discuss current advances to define the role of neutrophils-dependent oxidative stress in UC.

Keywords: 4-hydroxy-2-nonenal; dextran sodium sulfate; leukocytapheresis; neutrophill; ulcerative colitis.

Fig. 1

Neutrophil-endothelial interaction mediated by adhesion molecules and chemical mediators

Fig. 2

4-Hydroxyl-2-nonenal (HNE) protein adducts as a second messenger

Fig. 3

Effects of Mn-SOD on DSS-induced colitis in mice. Acute colitis was induced by DSS administered at 8% w/v in the drinking water in BALB/c female mice. MnSOD (50,000 U/kg) was dissolved in physiological saline, and administered by intraperitoneal injection for 7 days. Reprinted with permission [6].

Fig. 4

Luminol-dependent chemiluminescence in patients with ulcerative colitis. Reprinted with permission [22].

Fig. 5

Electron micrograph showing leukocytes, mostly neutrophils and monocytes adsorbed onto an Adacolumn cellulose acetate carrier. Photograph by Dr. A. Saniabadi of Japan Immunoresearch Laboratories.

Fig. 6

Granulocyte adsorptive apheresis therapy for steroid-refractory or -naïve ulcerative colitis. Reprinted with permission [32].