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Biomedical subjects

F L Harris

Publications and source records attributed to F L Harris.

11 recordsLinked to original sources
PubMed2001

Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand.

Neutrophils release soluble Fas ligand (sFasL), which can induce apoptosis in certain Fas-bearing cell types (Liles WC, Kiener PA, Ledbetter JA, Aruffo A, and Klebanoff SJ. J Exp Med 184: 429-440, 1996). We hypothesized that neutrophils could induce alveolar epithelial apoptosis via release of sFasL. A549 pulmonary adenocarcinoma cells expressed surface Fas and underwent cell death (10 +/- 7% viability) and DNA fragmentation (354 +/- 98% of control cells) when incubated with agonistic CD95/Fas monoclonal antibody (P < 0.05). Coincubation with human neutrophils induced significant A549 cell death at 48 (51 +/- 9% viability; P < 0.05) and 72 h (25 +/- 10%; P < 0.05) and increased DNA fragmentation (178 +/- 42% of control cells; P < 0.05), with morphological characteristics of apoptosis. The addition of antioxidants did not inhibit apoptosis. sFasL concentrations were maximally increased in coculture medium at 24 h (4.9 +/- 0.7 ng/ml; P < 0.05). Neutrophil-induced A549 cell apoptosis was blocked by inhibitory anti-Fas (42 +/- 6% of control cells; P < 0.05) and anti-FasL monoclonal antibodies (29 +/- 3%; P < 0.05). Human neutrophils and Fas similarly affected murine primary alveolar epithelial cell bilayers, and caspase activation occurred in response to Fas exposure. We conclude that neutrophils undergoing spontaneous apoptosis induce A549 cell death and DNA fragmentation, independent of the oxidative burst, that is mediated by sFasL.

Animals↗
PubMed2001

Chronic ethanol ingestion potentiates TNF-alpha-mediated oxidative stress and apoptosis in rat type II cells.

In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS). Because alveolar type II cell viability is critical for epithelial repair, our objective was to determine if chronic ethanol ingestion increased the sensitivity of type II cells to the inflammatory mediators upregulated during sepsis. In rats chronically fed ethanol, type II cell mitochondrial GSH was depleted, and tumor necrosis factor-alpha (TNF-alpha)-induced generation of mitochondrial reactive oxygen species (ROS) and apoptosis were potentiated. When added to the ethanol diet, the GSH precursor (-)-2-oxo-4-thiazolidinecarboxylic acid (Procysteine; Pro) but not N-acetylcysteine (NAC) normalized type II cell mitochondrial GSH. Likewise, Pro but not NAC normalized TNF-alpha-induced mitochondrial ROS and apoptosis. This suggested that chronic ethanol ingestion potentiated TNF-alpha-induced apoptosis in type II cells via mitochondrial GSH depletion. This may be particularly relevant in ARDS when type II cell viability is critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of ARDS patients with a history of alcohol abuse.

Alcohol Drinking↗
PubMed2001

Effect of chronic ethanol ingestion on alveolar type II cell: glutathione and inflammatory mediator-induced apoptosis.

BACKGROUND: In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome, a syndrome that requires alveolar type II cell proliferation and differentiation for repair of the damaged alveolar epithelium. We previously showed in a rat model that chronic ethanol ingestion decreased the antioxidant glutathione (GSH) in type II cells and exacerbated endotoxin-mediated acute lung injury. We hypothesized that this GSH depletion by ethanol, particularly mitochondrial GSH, predisposed type II cells to inflammatory mediator-induced apoptosis. METHODS: Adult male rats were fed the Lieber-DeCarli diet for 2, 6, or 16 weeks. Alveolar type II cells were then isolated and treated with hydrogen peroxide or TNF-alpha. The effect on glutathione (cytosolic and mitochondrial), apoptotic events, and necrosis were determined. In other studies, rats were fed ethanol for 6 weeks and were treated with endotoxin and apoptosis of type II cells determined by the TUNEL method. RESULTS: Chronic ethanol ingestion alone resulted in a progressive decrease in mitochondrial GSH and a progressive increase in the basal apoptosis and necrosis rate (p < or = 0.05). Furthermore, there was a progressive increase in the sensitivity of the cells to H2O2 or TNF-alpha induced cytochrome c release, caspase 3 activation, apoptosis, and necrosis (p < or = 0.05). Finally, there was a 2-fold increase in apoptotic type II cells in vivo when chronic ethanol ingestion was superimposed on endotoxemia. CONCLUSIONS: These results suggested that chronic ethanol ingestion resulted in a progressive depletion of mitochondrial GSH and sensitization of type II cells to inflammatory mediator-induced apoptosis and necrosis. These effects may be particularly relevant during acute stress when proliferation and differentiation of these cells are critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of acute respiratory distress syndrome in patients with a history of alcohol abuse.

Animals↗
PubMed1997

Ascorbate deficiency and oxidative stress in the alveolar type II cell.

The objective of this study was to determine the impact of limited ascorbate (Asc) availability on type II cell sensitivity to oxidant stress. Guinea pigs were fed diets with or without Asc for 18 days, and type II cells were isolated. Although lung Asc was decreased by 90% in deficient animals (scorbutic), type II cell Asc was decreased by 50%. Upon treatment with 250 microM H2O2, the necrotic injury was twofold greater in scorbutic cells compared with control cells. With 100 microM H2O2 treatment, apoptotic injury was twofold greater in scorbutic cells compared with control cells. Although there was less necrotic injury in cells exposed to 95% O2, the scorbutic cells were more sensitive than control cells. Asc pretreatment protected against necrosis and apoptosis. The Asc analog isoascorbate provided partial protection and suggested that part of the protection was not chemical detoxification but was Asc specific. We conclude that limited Asc availability resulted in a functional type II cell but a cell more sensitive to oxidant-induced injury.

Animals↗
PubMed1996

Glutathione supplements protect preterm rabbits from oxidative lung injury.

The main objective of this study was to determine if glutathione (GSH) supplementation attenuated hyperoxic lung injury. Preterm (29 days) rabbits were delivered and exposed for 24 h to 1) room air, 2) room air and GSH, 3) 95% oxygen and GSH. GSH supplements (1 mM) were delivered in the nutritional support of 10% dextrose and saline through a peritoneal catheter. Animals assigned to oxygen had decreased lung volumes at 35 cmH2O, decreased lung compliance, increased edema, decreased cell viability, and decreased lung tissue and lavage-reduced/oxidized GSH levels, compared with control animals. Despite exposure to hyperoxia, animals supplemented with GSH were not different from room air controls with respect to lung mechanics, edema, cell viability, or tissue and lavage GSH. These studies suggest that GSH supplementation maintains normal lavage and lung tissue GSH levels in preterm animals exposed to hyperoxia and attenuates the changes in lung mechanics associated with oxygen-induced lung injury.

Animals↗
PubMed1993

Blood-brain barrier penetration abolished by N-methyl quaternization of nicotine.

The present study determined the effect of organically quaternizing either of the two tertiary nitrogen sites of nicotine to assess the in vivo effects of the permanently ionized states of the synthesized N-[14C]methylnicotines on brain uptake in rat after intracarotid injection. Male Sprague-Dawley rats were used to measure the brain uptake index (BUI) by single-pass clearance in brain after rapid injection at pH 7.4 into the left common carotid artery (expressed as a percentage) relative to simultaneously injected 3HOH. The BUI of [14C]mannitol, a control for the method background, was measured to be 2.6 +/- 0.6. At physiological pH, in striking contrast to the [pyrrolidine-2-14C]nicotine BUI of 120 +/- 3, the N-[14C]-methylnicotines had a BUI of 3.0 +/- 0.6, which was not significantly different from the method background and which indicated abolition of blood-brain barrier penetration of nicotine with the sensitivity of the BUI method.

Animals↗
PubMed1987

Dilatation of bronchial stenosis with Gruentzig balloon.

Current treatments for bronchial stenosis include surgical resection, laser photoresections, cryotherapy, and limited experience with balloon dilatation. This article describes the use of the Gruentzig balloon for treatment of an acquired bronchial anastomotic stricture after sleeve resection for carcinoma.

Bronchial Diseases↗