Acute effect of cigarette smoke on cytoplasmic motility of alveolar macrophages in dogs

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in dogs in vivo. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time due to particle rotation (relaxation), which is thought to be inversely related to CM of AM (J. Appl. Physiol. 55: 1196-1202, 1983). The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to base-line values within 15 min. With the inhalation of the smoke of up to five cigarettes, peak lambda 0 was increased; with a further increase in the number of cigarettes, the effect of cigarette smoke decreased or disappeared. Nicotine injection and acetylcholine inhalation increased respiratory resistance to a degree similar to that observed with cigarette smoke but did not change lambda 0. However, either substance P (SP) or capsaicin injection increased lambda 0 in a fashion similar to that noted with cigarette smoke inhalation. Repeated administration of SP produced a significant tachyphylaxis of the effect, and capsaicin did not increase lambda 0 after the cigarette smoke-induced tachyphylaxis of the effect. Colchicine inhibited the cigarette smoke-induced increase in lambda 0. These results suggest that cigarette smoke increases CM of AM, probably through the release of tachykinins including SP from sensory nerves in the lung.     

Acute effects of cigarette smoke inhalation on peripheral airways in dogs

We studied the acute effects of the inhalation of cigarette smoke on the central and peripheral airways of 35 open-chested and tracheotomized dogs by the direct measurement of central (Rc) and peripheral (Rp) airway resistances. Rc was calculated by dividing the pressure difference between a tracheal catheter and a retrograde catheter by mouth flow, and Rp was obtained by dividing the pressure difference between the retrograde catheter and a pleural capsule by mouth flow. The pleural capsule was attached to the pleural surface for alveolar pressure measurement. Rc and Rp were measured by the 2-Hz forced oscillation method. With lung inhalation of the smoke of two-thirds of one cigarette in vagi intact dogs, Rp increased to 239% of the control value and Rc increased to 112%. After bilateral vagotomy, Rp increased to 143% and Rc increased to 104%. Propranolol did not influence the results. Hexamethonium and atropine both blocked these responses when vagi were intact. When the upper trachea, larynx, and nasopharynx, which were completely blocked by vagotomy, were exposed to the smoke of two-thirds of a cigarette, Rp increased to 155% and Rc increased to 144%. We thus conclude that cigarette smoke causes a major increase in Rp, mainly via the vagal reflex and partially via the stimulation of parasympathetic ganglia (probably nicotine), and a minor increase in Rc via vagal reflex.     

Acute inhalation of cigarette smoke augments hypoxic chemosensitivity in humans

Hypoxic and hypercapnic ventilatory responses were measured after two levels of acute inhalation of cigarette smoke, minimum-level nicotine smoke (smoke 1) and nicotine-containing smoke (smoke 2), in 10 normal men. Chemosensitivity to hypoxia and hypercapnia was assessed both in terms of slope factors for ventilation-alveolar PO2 curve (A) and ventilation-alveolar PCO2 line (S) and of absolute levels of minute ventilation (VE) at hypoxia or hypercapnia. Ventilatory response to hypoxia and absolute level of VE at hypoxia significantly increased from 23.5 +/- 22.6 (SD) to 38.6 +/- 31.3 l . min-1 . Torr and from 10.6 +/- 2.5 to 12.6 +/- 3.5 l . min-1, respectively, during inhalation of cigarette smoke 2 (P less than 0.05). Inhalation of cigarette smoke 2 tended to increase the ventilatory response to hypercapnia, and the absolute level of VE at hypercapnia rose from 1.42 +/- 0.75 to 1.65 +/- 0.58 l . min-1 . Torr-1 and from 23.7 +/- 4.9 to 25.5 +/- 5.9 l . min-1, respectively, but these changes did not attain significant levels. Cigarette smoke 2 inhalation induced an increase in heart rate from 64.7 +/- 5.7 to 66.4 +/- 6.3 beats . min-1 (P less than 0.05) during room air breathing, whereas resting ventilation and specific airway conductance did not change significantly. On the other hand, acute inhalation of cigarette smoke 1 changed none of these variables. These results indicate that hypoxic chemosensitivity is augmented after cigarette smoke and that nicotine is presumed to act on peripheral chemoreceptors.     

Acute effect of cigarette smoke on TNF-alpha release by macrophages mediated through the erk1/2 pathway

Pulmonary emphysema is a major cause of mortality and morbidity in chronic obstructive pulmonary disease (COPD). Cigarette smoking is a major risk factor in the development of pulmonary emphysema. In this study, we investigated the acute effect of cigarette smoke in vitro on the production of tumour necrosis factor-alpha (TNF-alpha) using differentiated U937 cells, a macrophage model system. We found that stimulation of the macrophages with cigarette smoke media (CSM) leads to a rapid activation of extracellular-regulated kinases 1 and 2 (erk1/2), p90RSK and a transient decrease in phosphorylation of PKB/akt. The CSM also caused the subsequent induction of TNF-alpha release. Our studies revealed that U0126, an inhibitor of the erk1/2 pathway, markedly suppressed CSM-induced TNF-alpha release. Consistent with this finding, U0126 blocked CSM-stimulated erk1/2 phosphorylation, as well as phosphorylation of the downstream kinase, p90RSK. On the other hand, the PI3-K inhibitor, LY294002, and epidermal growth factor receptor (EGFR)-specific inhibitor, AG1478, did not suppress the release of TNF-alpha. Thus, CSM induction of TNF-alpha production by differentiated macrophages is regulated primarily via the erk1/2 pathway.     

The cessation and detoxification effect of tea filters on cigarette smoke

To treat tobacco addiction,a tea filter was developed and studied for smoking cessation.This work reports the smoking cessation effect of tea when it was used as a component of cigarette filters.In one trial it was found that after using the tea filters for 2 months,the volunteer smokers decreased their cigarette consumption by 56.5%,and 31.7% of them stopped smoking.This work identified a new method and material,tea filter and theanine,which inhibit tobacco and nicotine addiction and provide an effective s...     

The effect of exposure to nicotine, carbon monoxide, cigarette smoke or cigarette smoke condensate on the mutagenicity of rat urine

Cigarette smokers have been reported to void urine which is more mutagenic than that voided by non-smokers, but the specific urinary mutagen(s) have not been identified. Since mechanistic studies are best performed in animal models, the objective of this study was to determine if a model to study the role of cigarette smoke and its components in urinary mutagenicity could be developed in rats. XAD-2 resin was used to concentrate the urine and the microsuspension modification of the Ames test used to quantify mutagenicity. Nicotine administered by intraperitoneal injection at 0.8 mg/kg (the maximum tolerated dose) or inhalation of carbon monoxide for 14 days at the maximum tolerated dose (1800 ppm, resulting in 68% carboxyhemoglobin) did not increase urinary mutagenicity. Cigarette smoke condensate (CSC) prepared by electrostatic precipitation of mainstream smoke increased urinary mutagenicity at doses of 100 and 200 mg/kg when administered acutely by either i.p. injection or gavage, verifying that the assay system was capable of detecting cigarette smoke-related mutagens in the urine. However, cigarette smoke administered by the appropriate route of exposure, nose-only inhalation, for 1, 7, 14 or 90 days (1 h per day) did not increase urinary mutagenicity. The smoke concentration administered was at or near the maximum tolerated dose as evidenced by carboxyhemoglobin concentrations of approximately 50%, and of 10% or more weight loss in exposed animals. Thus, although cigarette smoke condensate is mutagenic in vitro and mutagenic urine was observed when rats were given high doses of CSC by inappropriate routes of administration, acute or subchronic inhalation exposure to the maximum tolerated dose of whole cigarette smoke did not increase urinary mutagenicity in rats. These results indicate that the rat may be an inappropriate model to study urinary mutagenicity following the inhalation of tobacco smoke.     

Acute effect of cigarette smoke on TNF-α release by macrophages mediated through the erk1/2 pathway

Pulmonary emphysema is a major cause of mortality and morbidity in chronic obstructive pulmonary disease (COPD). Cigarette smoking is a major risk factor in the development of pulmonary emphysema. In this study, we investigated the acute effect of cigarette smoke in vitro on the production of tumour necrosis factor-α (TNF-α) using differentiated U937 cells, a macrophage model system. We found that stimulation of the macrophages with cigarette smoke media (CSM) leads to a rapid activation of extracellular-regulated kinases 1 and 2 (erk1/2), p90RSK and a transient decrease in phosphorylation of PKB/akt. The CSM also caused the subsequent induction of TNF-α release. Our studies revealed that U0126, an inhibitor of the erk1/2 pathway, markedly suppressed CSM-induced TNF-α release. Consistent with this finding, U0126 blocked CSM-stimulated erk1/2 phosphorylation, as well as phosphorylation of the downstream kinase, p90RSK. On the other hand, the PI3-K inhibitor, LY294002, and epidermal growth factor receptor (EGFR)-specific inhibitor, AG1478, did not suppress the release of TNF-α. Thus, CSM induction of TNF-α production by differentiated macrophages is regulated primarily via the erk1/2 pathway.     

Acute effects of cigarette smoke on breathing in rats: vagal and nonvagal mechanisms

The acute ventilatory response to inhalation of cigarette smoke was studied in anesthetized Sprague-Dawley rats. Cigarette smoke (6 ml, 50%) generated by a machine was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, a slowing of respiration resulting from a prolonged expiratory duration (173 +/- 6% of the base line; n = 32) was elicited in 88% of the rats studied. This initial inhibitory effect on breathing was not affected either by an increase (410%) in the nicotine content of the cigarette smoke or by pretreatment with hexamethonium (33 mg/kg iv). However, bilateral vagotomy completely eliminated the initial ventilatory inhibition. Cooling both vagi to 5.1 degrees C blocked the reflex apneic response to lung inflation, but it did not abolish the inhibitory effect of smoke. After the initial response, a rapid shallow breathing pattern developed and reached its peak 5-12 breaths after inhalation of high-nicotine cigarette smoke; this delayed response could not be prevented by vagotomy and was undetectable after inhalation of low-nicotine smoke. We conclude that the initial inhibitory effect of smoke on breathing is mediated by vagal bronchopulmonary C-fiber afferents, which are stimulated by smoke constituents other than nicotine, whereas the delayed tachypneic response to smoke is caused by the absorbed nicotine.     

Metals in cigarette smoke

Metals are vital for a huge number of physiological processes in the human body, but can also destroy health when the concentration is not within the physiologically favourable range. Cigarette smoking interferes with the carefully controlled metal homeostasis of the human body. This review focuses on the consequences of metal delivery to the human body by cigarette smoking and discusses the body's responses. The metal content of tobacco plants, smoke, the circulation, and various organs is discussed. Finally, we link individual cigarette smoke contained metals to the genesis of human diseases.     

Chemiluminescence of cigarette smoke.

Chemiluminescence from cigarette smoke (aerosol) and smoke "extracts" (suspensoids) are described. The emissons from aqueous and organic suspensoids persist for hours, are proportional to oxygen solubilities, possess energy of at least 1.8 electron volts, and display characteristics which suggest that the emissions may be partially sensitized by singlet oxygen.     

The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells

Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.     

The effect of cigarette smoke on influenza virus infection : A murine model system

Cigarette smoke was found to be toxic to the viability of influenza virus $\text{in vitro}$, but had no effect on the ability of the virus to hemagglutinate. Prolonged exposure of mice to cigarette smoke depressed the humoral immune response following infection with live influenza virus, and decreased the frequency of seroconversion. Conversely, short-term exposure of mice to cigarette smoke resulted in an enhancement of the immune response.     

Effects of cigarette smoke on the immune system

Although the health risks of tobacco smoking are well documented, there is increasing evidence that smokers have a lower incidence of some inflammatory and neurodegenerative diseases. Many of the adverse and beneficial effects of smoking might result from the ability of cigarette smoke to suppress the immune system. Nicotine, which is one of the main constituents of cigarette smoke, suppresses the immune system but might have therapeutic potential as a neuroprotective and anti-inflammatory agent.     

Stimulation of rapidly adapting receptors in canine lungs by a single breath of cigarette smoke

Inhalation of smoke generated from high-nicotine cigarettes frequently evoked an immediate augmented inspiration in conscious dogs (J. Appl. Physiol. 54: 562-570, 1983); this reflex response was believed to result from a stimulation of rapidly adapting receptors in the lungs. To test this hypothesis, we recorded the vagal afferent activity arising from the rapidly adapting receptors in the lungs and delivered 120 ml of high- and low-nicotine cigarette smoke separately in a single ventilatory cycle in 20 anesthetized open-chest and artificially ventilated dogs. These receptors were stimulated on the first breath of delivery of smoke generated by high-nicotine cigarettes; activity increased from a base line of 0.9 +/- 0.2 to a peak of 9.9 +/- 1.2 (SE) impulses/breath (n = 58). After three to six breaths when the receptors' discharge returned toward base-line activity, a delayed increase of activity emerged (peak activity = 3.4 +/- 0.6 impulses/breath, n = 58) in 32 of the 58 receptors studied and lasted for three to seven breaths. By contrast, only a mild stimulatory effect of low-nicotine cigarette smoke was found, either immediately or after a delay, in 15 of the 54 receptors studied. We conclude that rapidly adapting receptors are stimulated by a single breath of cigarette smoke and that nicotine is the primary stimulant agent.