Laima Taraseviciene-Stewart

Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth

Removal of apoptotic cells by neighboring viable cells or professional phagocytes is essential for the maintenance of tissue homeostastis. Here we show that the phagocytosis of apoptotic Jurkat T cells by mouse epithelial cells (HC‐11) and peritoneal macrophages leads to the secretion of growth and survival factors. We characterized VEGF as one of these factors which subsequently promote the proliferation of endothelial cells. Further we demonstrate that the phagocytosis of apoptotic bodies inhibits both spontanous and UV‐irradiation‐induced apoptosis in endothelial and epithelial cells. These effects were not observed when phagocytes had been exposed to viable or necrotic Jurkat T cells. We conclude that phagocytosis of apoptotic cells leads to secretion of growth and survival factors by phagocytes that represents a new form of life‐promoting cell‐cell interaction.

The expression of prostacyclin synthase is decreased in the small pulmonary arteries from patients with emphysema.

Abbreviations: PG prostaglandin; PGIS prostaglandin I2 synthase; VEGF vascular endothelial growth factor T here is growing evidence that the microvessels of the lung are involved in the pathobiology of emphysema and that the expression of vascular endothelial growth factor (VEGF), which has a vascular protective role, is decreased in the pulmonary arteries of patients with severe emphysema. The vascular protective effects of VEGF can be mediated through endothelial cell production of nitric oxide and prostacyclin (prostaglandin [PG] I2). PGI2 production in the lungs of patients with emphysema could be reduced as a consequence of reduced VEGF expression and/or other mechanisms. We wondered whether the expression of the gene encoding the critical enzyme PGI2 synthase (PGIS) was reduced in human emphysema lungs. We postulate that the decreased production of PGI2 is associated with the pulmonary vascular dysfunction observed in patients with emphysema. 6-keto-PGF1, the stable metabolite of PGI2, was measured by enzyme-linked immunosorbent assay in whole-lung tissue extracts. The expression of PGIS protein was measured by Western blotting in whole-lung tissue extracts and was assessed by immunohistochemistry of paraffin-embedded tissues. The messenger RNA expression of PGIS was measured by real-time reverse transcriptase polymerase chain reaction. 6-keto-PGF1 levels were significantly decreased in patients with emphysema. The main site of decreased expression by immunohistochemistry were small pulmonary arteries. The expression of PGIS protein measured by Western blotting was decreased in patients with emphysema compared to that in healthy lungs. The messenger RNA expression of PGIS was also decreased in the lungs of patients with emphysema. Decreased PGIS expression may contribute to pulmonary vascular dysfunction in patients with emphysema and may also signal a premalignant condition. The molecular mechanism by which PGIS messenger RNA expression is down-regulated in patients with emphysema needs further evaluation.

N-acetylcysteine treatment protects against VEGF-receptor blockade-related emphysema.

Administration of the VEGF receptor blocker SU5416 to rats causes alveolar septal cell apoptosis and emphysema; both can be prevented by a superoxide dismutase mimetic. Here we show that SU5416 induces the expression of heme oxygenase‐1 in the lung tissue and that administration of antioxidant N‐acetyl‐l‐cysteine protects alveolar septal cells against apoptosis, as demonstrated by caspase‐3 lung immunohistochemistry, and against emphysema.

Electronic Cigarettes Are as Toxic to Skin Flap Survival as Tobacco Cigarettes

Purpose Electronic cigarettes (e-cigarettes) have become increasingly popular. However, information about the health risks associated with e-cigarette use is sparse. Currently, no published studies examine the effects of chronic e-cigarette exposure on microcirculation or perfusion. Using a rat skin flap model, we examined the toxic microcirculatory effects e-cigarettes may have in comparison with tobacco cigarettes. Methods Fifty-eight rats were randomized to either exposure to room air, tobacco cigarette smoke, medium-nicotine content (1.2%) e-cigarette vapor, or a high-nicotine content (2.4%) e-cigarette vapor. After 4 weeks of exposure, a random pattern, 3 × 9 cm skin flap was elevated on the dorsum of the rats. At 5 weeks, flap survival was evaluated quantitatively, and the rats were euthanized. Plasma was collected for nicotine and cotinine analysis, and flap tissues were harvested for histopathological analysis. Results Evaluation of the dorsal skin flaps demonstrated significantly increased necrosis in the vapor and tobacco groups. The average necrosis within the groups was as follows: control 19.23%, high-dose vapor 28.61%, medium-dose vapor 35.93%, and tobacco cigarette 30.15%. Although the e-cigarette and tobacco cigarette groups did not differ significantly, each individual group had significantly more necrosis than the control group (P<0.05). These results were corroborated with histopathological analysis of hypoxic tissue. Conclusions Both the medium-content and high-nicotine content e-cigarette exposure groups had similar amounts of flap necrosis and hypoxia when compared with the tobacco cigarette exposure group. Nicotine-containing e-cigarette vapor is similarly toxic to skin flap survival as tobacco cigarettes.

The effects of electronic cigarette vapour on the lung: direct comparison to tobacco smoke

Electronic cigarette (e-cigarette) usage in the USA has drastically increased in the past 5 years due to age restrictions on conventional cigarettes, aggressive marketing and a perception that e-cigarettes are a healthy alternative. E-cigarettes contain nicotine, water, glycerol, propylene glycol and optional flavouring. On inhalation, the device heats the ingredients into a vapour [1]. While tobacco cigarette smoke is known to cause deleterious effects on the cardiovascular system, angiogenesis and skin capillary perfusion by causing direct injury to blood vessel walls, increased platelet aggregation, microvascular thrombosis [2–4] and inflammation [5], the consequences of e-cigarette vapour exposure on the lung are still largely unexplored [6, 7]. Recently, Lerner et al. [8] reported that vapours produced by e-cigarettes and e-cigarette fluids with flavourings induced toxicity, oxidative stress and inflammatory response in human bronchial airway epithelial cells (H292) and fetal lung fibroblasts (HFL1) as well as mouse lung. Garcia-Arcos et al. [9] showed that the aerosolised nicotine-containing e-cigarette fluid increased airway hyperreactivity, distal airspace enlargement, mucin production, and cytokine and protease expression in mice, implying potential dangers of nicotine inhalation during e-cigarette use. The inflammatory response to e-cigarette use involved increased neutrophil activation and mucus production [10], and decreased mucociliary clearance [11]. In human embryonic and mouse neural stem cells, human pulmonary fibroblasts [12], and skin and lung cells [13], cytotoxicity of e-cigarette vapour was correlated with the number and concentration of chemicals used to flavour the fluids. We recently showed in the skin flap survival model in vivo that nicotine-containing e-cigarette vapour is just as harmful to the microcirculation as tobacco cigarette smoke [4]. Electronic cigarettes are as toxic as tobacco cigarettes and can cause significant lung damage http://ow.ly/qT1l30ig1oR