Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability

Grisham, Matthew B.; Gaginella, Timothy S.; Ritter, Christoph von; Tamai, Hiroshi; Be, Rogers; Granger, D. Neil

doi:10.1007/bf00914274

Cited by 157 publications

(102 citation statements)

References 21 publications

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“…It is well known that during an inflammatory response hydrogen peroxide may be produced in sufficient quantities to overcome cellular defense mechanisms within localized areas, leading to tissue damage and amplification of leukocyte recruitment mechanisms. It is estimated that tissueresident neutrophils can generate local concentrations of 200-500 µM hydrogen peroxide within 60 min of stimulation [28]. Therefore, activated leukocytes can release superoxide radicals that are able to directly quench endogenous NO released by endothelial cells, a process known to result in endothelial dysfunction [22].…”

Section: Discussionmentioning

confidence: 99%

In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature

Scalia

Lefer

1998

Journal of Leukocyte Biology

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Abstract:The relationship between acute endothelial dysfunction and the extravasation of leukocytes was studied in vivo with intravital microscopy of the rat mesenteric microvasculature. Acute endothelial dysfunction of the rat mesenteric microvasculature was induced in vivo by superfusing the mesentery for 90 min with one of three different stimulating agents: N G -nitro-L-arginine methyl ester (L-NAME, 50 µM), thrombin (0.5 U/mL), or hydrogen peroxide (H 2 O 2 , 50 µM). All three agents induced a similar increase in leukocyte rolling and adherence, which was significantly greater than that observed in control rats superfused with KrebsHenseleit solution (P F 0.01). Transendothelial migration of leukocytes into the perivascular space was also increased by superfusion with L-NAME, thrombin, or H 2 O 2 . However, there was a greater increase in the number of migrated leukocytes in the rat mesentery after L-NAME and H 2 O 2 superfusion than that observed during thrombin superfusion. In vivo infusion of a neutralizing antibody against platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically inhibited L-NAMEinduced and H 2 O 2 -induced migration of leukocytes but did not prevent extravasation of leukocytes induced by thrombin. In rat mesenteries superfused with the three different stimuli, immunohistochemical analysis of endothelial cell adhesion molecules expressed on the microvascular endothelium revealed a significant increase of ICAM-1, but not PECAM-1, endothelial cell surface expression (P F 0.01 and P G 0.05 vs. control rats, respectively). Our data confirm a key role for PECAM-1 acutely in leukocyte extravasation in vivo and indicate that the involvement of constitutively expressed PECAM-1 in leukocyte transendothelial migration is preferentially correlated to oxidative stressrelated stimuli in the microvascular endothelium.

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Section: Discussionmentioning

confidence: 99%

In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature

Scalia

Lefer

1998

Journal of Leukocyte Biology

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“…Grisham and co-workers have shown that chloramines in general, and monochloramine in particular, are extremely effective promoters of increased vascular permeability, electrolyte loss, and epithelial cell loss in the rat colon [17]. Among the various oxidants tested, HOCl and NH 2 Cl had the most potent toxic effects at physiologically realistic concentrations.…”

Section: Chloramine Generationmentioning

confidence: 99%

“…Grisham's research team has also described the toxic effects on colonic mucosa of several chloramines, particularly monochloramine produced from the nonenzymatic reaction of hypochlorous acid (produced by activated neutrophils) and ammonia (produced by gut flora) [17]. Hydrogen peroxide formation in proximity to chloride ions, abundant in intestinal secretions, and certain peroxidases, especially myeloperoxidase (MPO) secreted into the extracellular medium by activated leukocytes, result in the formation of the hypochlorous acid, HOCl [18], a potent oxidant that is the active ingredient in household bleach:…”

Section: Chloramine Generationmentioning

confidence: 99%

Oxygen radicals in ulcerative colitis

Babbs

1992

Free Radical Biology and Medicine

270

169

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This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: ( l ) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.

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“…Although many inflammatory mediators secreted by these cells, including cytokines IL-1, IL-6, IL-8, IL-10, TNF- and leukotrienes together with luminal bacterial products such as bacterial lipopolysaccharide (LPS) and chemotactic peptide fMLP, have been implicated in the mucosal injury observed in IBD [3] , and the molecules that mediate tissue damage remain poorly understood [4][5][6][7] . Recent indirect evidence has, however, implicated reactive oxygen and nitrogen species (RONS) such as nitric oxide (NO), superoxide (O 2 -), peroxynitrite (ONOO -), hydrogen peroxide (H 2 O 2 ), and hypochlorite (OCl -) in the pathogenesis of mucosal lesion [8][9][10][11] . Rheum tanguticum Maxim ex Balf is a well-known traditional Chinese medicine especially for the treatment of gastrointestinal diseases.…”

Section: Introductionmentioning

confidence: 99%

Protective effects ofRheum tanguticumpolysaccharide against hydrogen peroxide-induced intestinal epithelial cell injury

Liu

Mei²,

Liu³

et al. 2005

WJG

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AIM:To describe the effect of Rheum tanguticum polysaccharide (RTP) on hydrogen peroxide-induced human intestinal epithelial cell injury. METHODS:Hydrogen peroxide (100 mol/L) was introduced to induce human intestinal epithelial cell injury. Cells were pretreated with RTP (30,100,300 g/mL) for 24 h before exposure to hydrogen peroxide. Cell viability was detected by MTT assay and morphological observation. Acridine orange staining and flow cytometry were performed to assess cell apoptosis. Lactate dehydrogenase (LDH) activity, production of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by spectrophotometry with corresponding assay kits. RESULTS:Following exposure to H 2 O 2 , a marked decrease in cell survival and SOD activity, increased production of MDA, LDH leakage and cell apoptosis were found. Pretreatment of the cells with RTP could significantly elevate cell survival, SOD activity and decrease the level of MDA, LDH activity and cell apoptosis.CONCLUSION: RTP may have cytoprotective and antioxidant effects against H 2 O 2-induced intestinal epithelial cell injury by inhibiting cell apoptosis and necrosis. This might be one of the possible mechanisms of RTP for the treatment of ulcerative colitis in rats.

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Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability

Cited by 157 publications

References 21 publications

In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature

In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature

Oxygen radicals in ulcerative colitis

Protective effects ofRheum tanguticumpolysaccharide against hydrogen peroxide-induced intestinal epithelial cell injury

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