Sidestream Cigarette Smoke Exposure Research Articles

Mainstream and sidestream cigarette smoke exposure increases Ca2+-dependent phospholipid binding proteins in guinea pig alveolar type II cells.

We have earlier identified the presence of a 36 kDa Ca2+-dependent phospholipid-binding protein (PLBP) in guinea pig alveolar type II cells. PLBP has been suggested to act as a mediator in facilitating and regulating intracellular surfactant assembly and delivery to the plasma membrane of type II cells for secretion into alveolar space. It has been reported that cigarette smoke exposure (CSE) causes a decrease in the surfactant activity in bronchial washings. We have also reported earlier that mainstream (MS) and sidestream (SS) CSE causes desensitization of beta-adrenoreceptors in guinea pig alveolar type II cells. Since both Ca2+ and beta-adrenoreceptors are involved in surfactant secretion and PLBP is involved in surfactant delivery, it is important to know whether CSE causes any change in the PLBP level in alveolar type II cells. In the present study, we have demonstrated that MS and SS CSE causes a significant increase in the levels of PLBP in alveolar type II cells (107 and 150%, respectively) and in lung lavage (42 and 125%, respectively) in comparison to that in sham control (430 ng/mg protein in alveolar type II cells and 780 ng/mg protein in lung lavage). The mechanism by which smoke exposure causes an elevation in the levels of PLBP in alveolar type II cells and lung lavage remains to be investigated.

Perinatal sidestream cigarette smoke exposure and the developing pulmonary surfactant system in rats.

1. Epidemiological studies have strongly implicated passive smoking with increased incidence of various respiratory diseases in children. Our earlier studies have shown that chronic exposure to tobacco smoke significantly changes the composition and the surface activity of the pulmonary surfactant in adult rats. The aim of the present study was to determine if perinatal exposure to sidestream cigarette smoke influences the composition and function of pulmonary surfactant system in developing rat pups. 2. Pregnant Sprague Dawley rats were exposed to sidestream cigarette smoke in a whole body exposure chamber for a total of 6 h each day and the pups born to these dams were further exposed to sidestream smoke for 2 h/day during postnatal period. Exposure of animals to smoke was ascertained by measuring their plasma cotinine. Surfactant analysis was performed on bronchoalveolar lavage fluids (BALF) collected from pups on postnatal day 1, 3, 7, 14, 21 and 35. The phospholipid (PL) content, percentage disaturated phosphatidylcholine (DSPC) and surfactant proteins (SP-A and SP-B) in BALF surfactant preparations from sham and smoke-exposed pups were compared. 3. Significant differences between the two groups were observed at two exposure points: a reduced level of SP-A on day 1, and, a higher level of SP-A and PLs on day 21, in smoke-exposed pups. Surface activity analysis of the surfactant films by pulsating bubble surfactometer did not show any significant differences between the sham and smoke-exposed groups at any exposure point. 4. The results indicate that perinatal exposure to sidestream smoke is capable of producing biochemical changes in the composition of pulmonary surfactant at different stages of development but these changes do not influence surface tension reducing properties of the surfactant.

Effects of extended sidestream smoke exposure on components of the C-fiber axon reflex

We have previously shown that young guinea pigs repeatedly exposed to sidestream cigarette smoke (SS) develop decreased airway reactivity of the C-fiber system without changing reactivity to one of its neurotransmitters, substance P (SP). This study was designed to determine whether the decreased reactivity was due to decreased responsiveness to another neurotransmitter, neurokinin A (NKA), decreased lung SP content, decreased affinity or number of NK 1 receptors, and/or decreased number of C-fibers. Duncan Hartley guinea pigs were exposed to filtered air (FA) or to SS for 6 h/day, 5 days/week for 5 weeks starting at 1 week of age. SS exposure did not change, (1) airway reactivity to NKA injected into the pulmonary artery of their isolated perfused lungs ( n = 6–7 each group), (2) lung SP content as measured by enzyme immunoassay ( n = 12 each group), (3) NK, receptor number or affinity as measured by radioligand binding ( n = 7 each group), or (4) SP-immunoreactive nerve profiles of the terminal bronchioles or small airways ( n = 6 each group). Thus, SS exposure does not decrease C-fiber system by reducing NKA responsiveness, decreasing SP content, changing NK 1 receptors, or decreasing the number of C-fibers.

In Utero and Postnatal Effects of Sidestream Cigarette Smoke Exposure on Lung Function, Hyperresponsiveness, and Neuroendocrine Cells in Rats

We evaluated whether sidestream smoke (SS) exposure in utero and/or postnatally causes airway obstruction and hyperresponsiveness, and whether the effect is associated with neuroendocrine cell hyperplasia. Pregnant Sprague-Dawley rats were exposed to filtered air (FA) or to SS (total suspended particulate concentration, 1.00 +/- 0.07 mg/m3, CO, 4.9 +/- 0.7 ppm; nicotine, 344 +/- 85 micrograms/m3; mean +/- SD) for 4 hr/day, 7 days/week from Day 3 of gestation until birth and then their female pups were exposed to either FA or SS for 7-10 weeks postnatally. This resulted in four exposure conditions: in utero FA followed by postnatal FA (FA/FA), in utero FA followed by postnatal SS (FA/SS), in utero SS followed by postnatal FA (SS/FA), and in utero SS followed by postnatal SS (SS/SS). The lungs from the pups (n = 6-8 of each exposure combination) were then placed in an isolated buffer-perfused system where transpulmonary pressure, airflow, and pulmonary artery pressure (Ppa) were measured while increasing doses of methacholine were injected into the pulmonary artery. Three lungs from each group were then fixed in 1% paraformaldehyde and neuroendocrine cells were identified immunohistochemically using antibodies to neuron-specific enolase. As compared to lungs from FA/FA-exposed rats, lungs from SS/SS-exposed rats exhibited 24% lower Cdyn (p = 0.0006, ANOVA), greater reactivity to methacholine (p = 0.0001, repeated measures ANOVA), and more neuroendocrine cells per centimeter basal lamina (p = 0.0006, ANOVA). Lungs from SS/FA- or FA/SS-exposed rats were not different from lungs from FA/FA-exposed rats in any of these parameters. We conclude that exposure to SS both pre- and postnatally (but not only pre- or only postnatally) results in lungs which are less compliant, more reactive to methacholine, and have a greater number of neuroendocrine cells.

Mainstream and sidestream cigarette smoke exposure increases retinol in guinea pig lungs

We have studied in guinea pigs the effects of cigarette smoke exposure on vitamin A (retinol) levels in plasma, lung, lung lavage, and liver. Smoke was generated from 1R3F cigarettes in a smoke exposure instrument designed by University of Kentucky Tobacco and Health Research Institute. Three-week-old male guinea pigs were exposed to mainstream, sidestream, or sham smoke, generated twice daily from three cigarettes for 6 weeks. In addition, some animals were kept as room controls for some time. After 6 weeks of smoke exposure, some animals were allowed to recover for 6 weeks without smoke. After 6 weeks of smoking, the plasma retinol levels were lower in both smoke exposed groups when compared to the values in the sham group. Furthermore, in comparison to the sham group, the mainstream and sidestream smoke exposed groups showed a 7.6- and 8.3-fold increase in the levels of lung retinol, respectively. After the 6-week recovery period, plasma retinol of both smoke-exposed groups reached the control levels. In contrast, withdrawal of smoking did not show such an effect on the lung retinol level in both mainstream or sidestream groups. Electronmicroscopy of the lungs showed deleterious alterations in the morphology of the lungs in both mainstream and sidestream groups. Although the mechanism(s) involved in the elevation of retinol content of the lung due to smoke exposure remains to be elucidated, it is of interest that elevation of retinol content and alteration of lung morphology occurred not only in the mainstream smoke exposed but also in the sidestream group.

The effect of mainstream and sidestream cigarette smoke exposure on oxygen defense mechanisms of guinea pig erythrocytes.

We have studied the effects of short-term exposure of guinea pigs to cigarette smoke under both mainstream (MS) and sidestream (SS) conditions on the activities of major antioxidant enzymes and lipid peroxidation potential of erythrocytes. The smoke-exposed groups had an increase in the activity of superoxide dismutase (SOD), a decrease in the activities of glutathione peroxidase (GSH-Px) and NADPH generating enzymes, and no change in the activity of catalase. Furthermore, there was a significant increase in the in vitro lipid peroxidation potential of erythrocytes in both MS- and SS-exposed groups. However, the lipid peroxidation potential was higher in the MS-exposed group than that in the SS-exposed group.

Chronic Sidestream Cigarette Smoke Exposure Causes Lung Injury in Rabbits

The effects of sidestream cigarette smoke (SSCS) (a 15-min exposure per day for 20 days) were determined on markers of lung injury in New Zealand white rabbits (n = 9) and a control group (n = 6). The SSCS consisted of air and smoke which were aspirated by syringe from a funnel inverted over a lit ciga rette. The rabbits were placed in an environmental chamber into which 3 liters of SSCS were injected over a 15-min period each day. Chronic SSCS caused an increase (p < 0.05) in pulmonary epithelial clearance (k) of technetium labeled diethylenetriamine pentaacetate (99mTcDTPA); k = 0.83 (±0.07) for the SSCS-exposed group and 0.66 (± 0.02) for the control group. This increase in lung permeability was accompanied by an increase in bronchoalveolar lavage (BAL) white cell count; SSCS = 83,353 ( ± 11,954) cells/mm3 BAL fluid versus control = 16,450 (± 6,683) cells/mm3 BAL fluid and an increase in BAL leukotriene E4; SSCS = 742 (± 285) pg/ml BAL fluid compared with 76 (± 2) pg/ml BAL fluid for controls. Cultured...

Sidestream cigarette smoke-exposure of mouse cells induces cell stress/heat shock-like proteins

Specific alterations in cellular protein synthesis have been identified in mouse L929 and B16 cells exposed to “passive” (sidestream) smoke freshly generated from unfiltered cigarettes. A decrease in both cell viability and protein synthesis was observed in monolayer cell cultures following exposure to increasing numbers (0–12) of puffs of sidestream smoke. With exposures that resulted in approximately 30% or higher loss in cell viability, there was an apparent induction of cell stress/heat shock-like polypeptides with approximate molecular weights of 88 000, 66 000 and 23 000. After exposure to higher numbers of puffs that led to a loss of cell viability of 80% or greater, a different set of polypeptides was synthesized, including a major new protein of 38 000 mol. wt and 2 other predominant proteins of 45 000 and 30 000 mol. wt. The same specific effects on cellular protein synthesis were also observed after exposure to a similar number of puffs of the gas phase of sidestream cigarette smoke (minus the particulate phase components).