Cigarette smoke extract may induce lysosomal storage disease‐like adverse health effects

Abstract

Cigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH‐S, a mouse alveolar macrophage cell line. CSE decreased cell viability accompanying increased lactate dehydrogenase release. Additionally, mitochondrial volume and the potential increased along with enhanced expression of mitochondrial fusion proteins and decreased adenosine triphosphate production. Similarly, CSE clearly induced increase of catalase activity and intracellular calcium concentration and decrease of endoplasmic reticulum and lysosome volume at the highest dose. More interestingly, damaged organelles accumulated in the cytosol, and CSE‐containing particles specifically penetrated to mitochondria. Meanwhile, any significant change in autophagy related protein expression was not found in CSE‐treated cells. Subsequently, we evaluated the effects of CSE on secretion of inflammatory related cytokines and chemokines, considering the relationship between organelle damage and the disturbed immune response. Very importantly, we found that expression of innate and adaptive immunity related mediators is disrupted following CSE exposure. Taken together, we suggest that CSE may cause the accumulation of damaged organelles in the cytoplasm by impairing selective autophagic function. In addition, this accumulation is responsible for the inadequate ability of immune cells to repair the damage of lung tissue following exposure to CSE.

Transcriptomics Analysis Identifies the Presence of Upregulated Ribosomal Housekeeping Genes in the Alveolar Macrophages of Patients with Smoking-Induced Chronic Obstructive Pulmonary Disease

“…Although it has been well-recognized that cigarette smoke is the most common cause of COPD, the specific mechanisms responsible have not yet been elucidated. 16 , 17 This study analyzed the last 15 years of datasets (until August 2020) available from the GEO database, and found that there was an extensive and significant degree of gene differential expression of AM between the COPD smoking and non-COPD smoking group. It was found that people with COPD have a number of significantly differently expressed genes related to energy metabolism or oxidative stress than those without COPD.…”

Smoking is associated with increased eryptosis, suicidal erythrocyte death, in a large population-based cohort

“…Inhaled tobacco smoke comprises substances such as carbon monoxide (CO), formaldehyde, acetaldehyde, benzopyrenes, and nicotine which can enter the circulation 3 , 4 . Most of these substances are toxic and can cause tissue damage by inducing oxidative stress and inflammation 5 – 7 . In addition, CO binds to hemoglobin to form carboxyhemoglobin which reduces oxygen-carrying capacity and oxygen utilization 8 .…”

The Effects of Naringin on Cigarette Smoke-Induced Dynamic Changes in Oxidation/Antioxidant System in Lung of Mice

“…2 CS contains more than 4000 chemicals, many of which have been associated with deleterious health consequences. 3 Particularly, oxidants, such as nicotine, acrolein, and carbon monoxide, can be detrimental. 4 Oxidative damage resulting from oxidants of CS, such as nitric oxide and carbonyls, plays major roles in the development of many tobacco-caused diseases including respiratory and heart diseases, cancers, and others.…”