Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration

Abstract

The objective of this study was to determine whether hydrogen peroxide, iron, and/or hydroxyl radicals play a role in ischemia/reperfusion (I/R)-induced granulocyte infiltration in the feline small intestine and whether a chemoattractant is formed when superoxide or hydrogen peroxide reacts with feline extracellular fluid. In vivo determinations of granulocyte infiltration consisted of measurements of tissue myeloperoxidase activity in either the intestinal mucosa (I/R studies) or dermis (chemotaxis studies), whereas in vitro measurements of granulocyte migration were obtained using a Boyden chamber. Treatment with either catalase or the iron chelator deferoxamine significantly attenuated granulocyte infiltration into the mucosa induced by reperfusion of the ischemic intestine. Two hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU), were also evaluated for their ability to modulate I/R-induced granulocyte infiltration. DMTU significantly attenuated the I/R-induced granulocyte accumulation, whereas DMSO had no effect. In other experiments, we were unable to stimulate granulocyte migration with feline plasma exposed to superoxide-generating systems using both in vitro and in vivo models of leukocyte chemotaxis. However, hydrogen peroxide in the presence of either ferrous iron or hemoglobin did significantly increase the chemotactic activity of cat plasma. The results obtained from our studies suggest that either hydrogen peroxide or radical species derived from the interaction of superoxide and hydrogen peroxide with iron elicit I/R-induced granulocyte infiltration in the intestine.

Effects of beta-glucan on hepatic damage caused by obstructive jaundice

“…Ayrıca nötrofil infiltrasyonu ile MPO aktivitesi arasında korelasyon mevcuttur ve MPO aktivitesinin yüksek olması nötrofil infiltrasyonunu ve doku hasarı fazlalığını göstermektedir. [13][14][15][16][17] Bazı çalış-malarda TS'de karaciğerde ve uzak organlarda nötro-fil infiltrasyonunun olduğu, dolayısıyla MPO aktivitesinin arttığı gösterilmiştir. [2,18] Şener ve arkadaşları-nın [19] çalışmasında bası ülseri oluşturulan sıçanlarda, beta glukanın, MPO düzeyini düşürdüğü tespit edilmiştir.…”

Replenishment of Glutathione Levels Improves Mucosal Function in Experimental Acute Colitis

“…Thus, stimulated inflammatory cells present in the inflamed mucosa are capable of producing superoxide anion and hydrogen peroxide (Harris et al, 1992;McKenzie et al, 1996;Simmonds and Rampton, 1993).The xantine oxidase pathway and the oxidation of arachidonic acid in colonocytes constitute additional sources of ROS (Biemond et al, 1988;Markowitz et al, 1988;Sedghi et al, 1993). The interaction of these species with specific vascular or interstitial components yield potent chemoattractants for inflammatory phagocytes, establishing a self-amplifying cycle of ROS production that may overwhelm defense strategies resulting in tissue damage (Lewis et al, 1988;Shingu and Nobunaga 1984;Zimmerman et al, 1990).…”

“…Thus, stimulated inflammatory cells present in the inflamed mucosa are capable of producing superoxide anion and hydrogen peroxide (Harris et al, 1992;McKenzie et al, 1996;Simmonds and Rampton, 1993).The xantine oxidase pathway and the oxidation of arachidonic acid in colonocytes constitute additional sources of ROS (Biemond et al, 1988;Markowitz et al, 1988;Sedghi et al, 1993). The interaction of these species with specific vascular or interstitial components yield potent chemoattractants for inflammatory phagocytes, establishing a self-amplifying cycle of ROS production that may overwhelm defense strategies resulting in tissue damage (Lewis et al, 1988;Shingu and Nobunaga 1984;Zimmerman et al, 1990).One of the most commonly used experimental models of IBD is the administration of an enema containing the contact-sensitizing allergen trinitrobenzenesulfonic acid (TNBS) in ethanol resulting in the development of macroscopic, histologic, and biochemical alterations that are well-characterized (Rachmilewitz et al, 1989;Wallace, 1988;Wallace et al, 1989). Although the mechanisms whereby TNBS cause an inflammatory response are not completely defined, this response is thought to be initiated by macrophagemediated recognition and degradation of the TNBSmodified cells and proteins within the colonic interstitium (Grisham et al, 1991;Kunin and Gallily, 1983).…”

Nitric oxide as a regulator of inflammatory processes

“…The anti-oxidant capacity of plasma was found to be doubled by the administration of NO donors. Moreover, these concentrations of the NO donors prevented reperfusion-induced mucosal injury, which has been shown to be mediated in large part by reactive oxygen metabolites (Perry et al 1986, Zimmerman et al 1990. A mechanism for superoxide anion scavenging by NO has not been clearly delineated.…”