Inflammatory response of lung macrophages and epithelial cells to tobacco smoke: a literature review of ex vivo investigations

Abstract

Chronic inflammation contributes to the initiation and progression of tumors and tobacco smoke-associated inflammation is associated with malignant and certain non-neoplastic lung diseases. Reported herein are the results of an interpretative synthesis review of the literature assessing the inflammatory response of lung macrophages (MPhi) and epithelial cells to tobacco smoke as measured ex vivo. Papers were retrieved using Boolean operations from PubMed and Scopus. Many writings reported the results of assays of human MPhi from fresh surgically excised human lung tissue, bronchoalveolar lavage, activated blood monocytes, long-term cell lines and MPhi from different laboratory animals. Some publications reported the findings of comparative studies of lung MPhi freshly isolated from the lungs of smokers and non-smokers. Other papers described the effect of tobacco smoke on lung epithelial cells. Most investigators quantified the response of the target cells to tobacco smoke by measuring the production of pro-inflammatory mediators; these included chemokines, cytokines, reactive oxygen species and enzymes. Investigators have reported conflicting observations of the response of human and animal MPhi and epithelial cells to tobacco smoke. The spectrum included papers describing robust production of various inflammatory mediators, significant reduction of a pro-inflammatory response to a known stimulant and overt cytotoxicity. This literature review documents that there exists no consensus, and no emerging trend line, of the reproducible effect(s) of cigarette smoke. This discrepancy reflects the absence of standardized protocols for collecting, processing and bioassaying the smoke, a highly complex aerosol, and identifies the need for establishing collaborative research schemes.

Effects of cigarette smoking on circulating leukocytes and plasma cytokines in monozygotic twins

“…To overcome some of these limitations, and to reduce possible data dispersion due to differences in genetic background and lifestyle, we investigated the effects of cigarette smoking on several immune parameters in healthy smoking-discordant twins: one a smoker and the other a non-smoker. The influence of smoke on leukocyte cell numbers and cell function has been demonstrated in several previous studies and our results are consistent with these findings [9,[32][33][34][35]. On the contrary, data concerning the influence of smoking on lymphocyte subpopulations are conflicting [35][36][37][38].…”

Cigarette Smoke Extract (CSE) Delays NOD2 Expression and Affects NOD2/RIPK2 Interactions in Intestinal Epithelial Cells

“…Loss of NFκB activation and NFκB-dependent gene responses against pathogenic bacteria in the gut might be detrimental. Smoking may also interfere with other mechanisms that also activate NFκB in the presence of bacteria, possibly by mechanisms of oxidative stress [54] or through toll-like receptors [55].…”

Mitochondria dysfunction: A novel therapeutic target in pathological lung remodeling or bystander?

“…Characterization of macrophages from COPD patients with a history of chronic cigarette smoke exposure revels a unique phenotype with impaired phagocytic activity and upregulation of M2 markers which contribute to tissue remodeling through production of metalloproteases (Woodruff, et al, 2005, Smith, Paszkiewicz, Hutson, & Pauly, 2010and Shaykhiev, et al, 2009). Metabolism plays a key role in regulating macrophage function with M1 cells deriving energy from glycolysis which can also be diverted to generate ROS during respiratory burst to facilitate bacterial killing whereas M2 polarized cells derive energy from fatty acid synthesis and oxidative metabolism providing the M2 cell with a sustainable source of energy for its important secretory functions (Mantovani, Biswas, Galdiero, Sica, & Locati, 2013).…”