Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae

ABSTRACT Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.

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In Vivo Versus In Vitro Airway Surface Liquid Nicotine Levels Following Cigarette Smoke Exposure

Journal of Analytical Toxicology ◽

10.1093/jat/32.3.201 ◽

2008 ◽

Vol 32 (3) ◽

pp. 201-207 ◽

Cited By ~ 47

Author(s):

L. A. Clunes ◽

A. Bridges ◽

N. Alexis ◽

R. Tarran

Keyword(s):

Cigarette Smoke ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Airway Surface Liquid ◽

Surface Liquid

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Abstract 14445: Reduced Expression of Let-7f Leads to Impaired Ischemia-Induced Neovascularization Following Cigarette Smoke Exposure: Role of ALK5/SMAD2/PAI-1 Pathway

Circulation ◽

10.1161/circ.132.suppl_3.14445 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Wahiba Dhahri ◽

Sylvie Dussault ◽

Paola Haddad ◽

Julie Turgeon ◽

Sophie Tremblay ◽

...

Keyword(s):

Cigarette Smoke ◽

Capillary Density ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Mirna Array ◽

And Function ◽

Pai 1

Background: Exposure to cigarette smoke is associated with impaired formation of new blood vessels (neovascularization) in response to ischemia. Here we investigated the potential role of miRs in that physiopathology. Methods and Results: Using Affimetrix GeneChip miRNA array analysis, we identified let-7f as a pro-angiogenic miR which expression is reduced following cigarette smoke exposure. qRT-PCR analyses confirmed that the expression of let-7f is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischemia, intramuscular injection of let-7f mimic restored ischemia-induced neovascularisation in MES. At day 21 after ischemia, Doppler flow ratios and capillary density in ischemic muscles were significantly improved in MES treated with let-7f mimic compared to those treated with a mimic control. Clinically, mice treated with let-7f mimic also exhibited reduced ambulatory impairment and hindlimb ischemic damages. Interestingly, we found that treatment with let-7f mimic can rescue endothelial progenitor cell (EPC) number and function (migration, integration into tubules) in MES. Let-7f has previously been shown to target ALK5 (TGF-βRI), an important modulator of angiogenesis. We found that ALK5 is significantly increased in HUVECs exposed to CSE and in the ischemic muscles of MES. This is associated with a downstream activation of anti-angiogenic factors such as SMAD2 and PAI-1. Importantly, treatment with let-7f mimic reduces the expression of ALK5, SMAD2 and PAI-1 both in vitro and in vivo. Moreover, let-7f mimic can also rescue angiogenesis in HUVECs exposed to CSE. Conclusion: Cigarette smoke exposure is associated with reduced expression of let-7f, which leads to impaired neovascularization following ischemia. Our results suggest that the mechanism involves increased activation of ALK5, together with a downstream stimulation of the anti-angiogenic SMAD2/PAI-1 pathway. Overexpression of let-7f using a miR mimic could constitute a novel therapeutic strategy to improve ischemia-induced neovascularization in pathological conditions.

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Mouse Protocadherin-1 Gene Expression Is Regulated by Cigarette Smoke Exposure In Vivo

PLoS ONE ◽

10.1371/journal.pone.0098197 ◽

2014 ◽

Vol 9 (7) ◽

pp. e98197 ◽

Cited By ~ 7

Author(s):

Henk Koning ◽

Antoon J. M. van Oosterhout ◽

Uilke Brouwer ◽

Lisette E. den Boef ◽

Renée Gras ◽

...

Keyword(s):

Gene Expression ◽

Cigarette Smoke ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Exposure In Vivo

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Retinal tissue develops an inflammatory reaction to tobacco smoke and electronic cigarette vapor in mice

Journal of Molecular Medicine ◽

10.1007/s00109-021-02108-9 ◽

2021 ◽

Author(s):

Feng Wang ◽

Stefan Hadzic ◽

Elsa T. Roxlau ◽

Baerbel Fuehler ◽

Annabella Janise-Libawski ◽

...

Keyword(s):

Cigarette Smoke ◽

Exposure Time ◽

Inflammatory Reaction ◽

Smoke Exposure ◽

Age Related Macular Degeneration ◽

Controlled Study ◽

Cigarette Smoke Exposure ◽

List Type ◽

Retinal Tissue

Abstract Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative to conventional cigarettes (C-cigarette), electronic cigarettes (E-cigarette) have been globally promoted and are currently widely used. The increasing usage of E-cigarettes raises concerns with regard to short- (2 weeks), medium- (3 months), and long- (8 months) term consequences related to retinal tissue. In this report, a controlled study in mouse models was conducted to probe the comprehensive effects of E-cigarette vapor on retina, retinal pigmented epithelium (RPE), and choroidal tissues by (1) comparing the effects of C-cigarette smoke and E-cigarette vapor on retina separately and (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory (IL-1β, TNFα, iNOS) and angiogenic (VEGF, PEDF) mediators in retina/RPE/choroid by ELISA assays. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid as compared to retinal tissue, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might also be related to the onset of wet AMD in humans. Key messages C-cigarette smoke exposure promotes an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor develop inflammatory and angiogenic reactions more pronounced in RPE and choroid compared to retinal tissue, while nicotine-containing E-cigarette vapor causes even a more serious reaction. Both inflammatory and pro-angiogenic reactions increase with the extension of E-cigarette vapor exposure time.

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Prenatal cigarette smoke exposure slightly alters neurobehavioral development in neonatal rats: Implications for developmental origins of health and disease (DoHAD)

Physiology International ◽

10.1556/2060.2020.00007 ◽

2020 ◽

Vol 107 (1) ◽

pp. 55-66

Author(s):

B. Mammel ◽

T. Kvárik ◽

Zs. Szabó ◽

J. Gyarmati ◽

T. Ertl ◽

...

Keyword(s):

Cigarette Smoke ◽

Motor Coordination ◽

Smoke Exposure ◽

Whole Body ◽

Cigarette Smoke Exposure ◽

Control Group ◽

Developmental Origins ◽

Smoking During Pregnancy ◽

Neurobehavioral Development ◽

Health And Disease

AbstractNumerous studies indicate that smoking during pregnancy exerts harmful effects on fetal brain development. The aim of this study was to determine the influence of maternal smoking during pregnancy on the early physical and neurobehavioral development of newborn rats. Wistar rats were subjected to whole-body smoke exposure for 2 × 40 min daily from the day of mating until day of delivery. For this treatment, a manual closed-chamber smoking system and 4 research cigarettes per occasion were used. After delivery the offspring were tested daily for somatic growth, maturation of facial characteristics and neurobehavioral development until three weeks of age. Motor coordination tests were performed at 3 and 4 weeks of age. We found that prenatal cigarette smoke exposure did not alter weight gain or motor coordination. Critical physical reflexes indicative of neurobehavioral development (eyelid reflex, ear unfolding) appeared significantly later in pups prenatally exposed to smoke as compared to the control group. Prenatal smoke exposure also resulted in a delayed appearance of reflexes indicating neural maturity, including hind limb grasping and forelimb placing reflexes. In conclusion, clinically relevant prenatal exposure to cigarette smoke results in slightly altered neurobehavioral development in rat pups. These findings suggest that chronic exposure of pregnant mothers to cigarette smoke (including passive smoking) results in persisting alterations in the developing brain, which may have long-lasting consequences supporting the concept of developmental origins of health and disease (DoHAD).

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Mouse Parenchymal Fibroblasts Are Intrinsically Different From Large And Small Airway Fibroblasts And Also Differ In Their Response After In Vivo Cigarette Smoke Exposure

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a3876 ◽

2010 ◽

Author(s):

Olena Preobrazhenska ◽

Joanne L. Wright ◽

Andrew Churg

Keyword(s):

Cigarette Smoke ◽

Smoke Exposure ◽

Small Airway ◽

Cigarette Smoke Exposure

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Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure

Neuroscience Letters ◽

10.1016/j.neulet.2018.05.045 ◽

2018 ◽

Vol 682 ◽

pp. 1-9 ◽

Cited By ~ 19

Author(s):

Mohammad A. Kaisar ◽

Farzane Sivandzade ◽

Aditya Bhalerao ◽

Luca Cucullo

Keyword(s):

Cigarette Smoke ◽

Vascular Endothelium ◽

Cellular Response ◽

Electronic Cigarettes ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Detoxifying Enzymes ◽

The Brain ◽

Gender Specific

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Humic-like substances in cigarette smoke condensate and lung tissue of smokers

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.266.4.l382 ◽

1994 ◽

Vol 266 (4) ◽

pp. L382-L388 ◽

Cited By ~ 6

Author(s):

A. J. Ghio ◽

J. Stonehuerner ◽

D. R. Quigley

Keyword(s):

Free Radical ◽

Cigarette Smoke ◽

Lung Tissue ◽

Cigarette Smoke Exposure ◽

Cigarette Smoke Condensate ◽

Free Radical Generation ◽

Carboxylate Content ◽

Radical Generation

Deposition of pigmented matter in the lower respiratory tract correlates with the extent of emphysema in smokers as well as with free radical generation and iron accumulation. Pulmonary emphysema is postulated to be mediated by free radical generation which is either directly or indirectly associated with cigarette smoke exposure. The hypothesis was tested that 1) incomplete combustion of tobacco yields humic-like substances (HLS) which 2) deposit in the lung as pigmented particulates, 3) complex iron cations in vitro and in vivo, and 4) have a capacity to catalyze oxidant formation. HLS, isolated by alkali extraction of cigarette smoke condensate (CSC) (Tobacco Health Research Institute, University of Kentucky), demonstrated a high carbon and low carboxylate content on elemental and functional group analyses, respectively, compared with values for HLS sequestered from soils. The HLS isolated from CSC had a capacity to complex iron in vitro and accumulated the metal in vivo after intratracheal instillation in an animal model. Both HLS and its iron complex generated free radicals, and some portion of this oxidant generation was metal dependent. Lung tissue collected at autopsy from smokers contained HLS with an infrared spectrum almost identical to that of the material isolated from CSC. Associations between particulate deposition, metal accumulation, and free radical generation suggest a possible role of HLS in the induction of lung disease following cigarette exposure.

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