Featured Article: Endothelial disruptive pro-inflammatory effects of nicotine and e-cigarette vapor exposures

Featured Article: Available for free download (http://ajplung.physiology.org/) even by those with no subscription to APS journals 

Endothelial disruptivepro-inflammatory effects of nicotine and e-cigarette vapor exposures

Kelly S Schweitzer , Steven X Chen , Sarah Law , Mary J Van Demark , Christophe Poirier , Matthew J Justice , Walter C Hubbard , Elena S Kim , Xianyin Lai , Mu Wang , William D. Kranz, Clinton J. Carroll , Bruce D. Ray , Robert Bittman , John Goodpaster , Irina Petrache

American Journal of Physiology - Lung Cellular and Molecular Physiology Published 15 May 2015 Vol. no. , DOI: 10.1152/ajplung.00411.2014

It is well known that cigarette smoking is the primary cause of chronic obstructive lung disease and contributes to the development of atherosclerosis and cardiovascular disease.  During the last two years, AJP-Lung has published about 60 papers documenting the potential mechanisms by which cigarette smoke damage every components of the respiratory system by a variety of mechanisms (PubMed search: Am J Physiol Lung Cell Mol Physiol. AND cigarette smoke AND (2012 OR 2013 OR 2014 OR 2015). The classical studies of Church and Pryor (see Environ Health Perspect. 1985 Dec; 64: 111–126) showed that the  vapor phase of cigarette  smoke contains a large number of highly reactive oxygen, nitrogen and carbon centered radicals (generated by the combustion of tobacco leaves; Indoor Air. 2005 Apr;15(2):135-40.) while the tar phase contains quinone/hydroquinone which is capable of reducing oxygen to generate reactive oxygen and nitrogen species.  In addition cigarette smoke contains a mixture of more than 5,000 toxic chemicals, including nicotine and acrolein; Int J Environ Res Public Health. 2011 Feb; 8(2): 613–628).

However, the possible hazards of electronic-cigarette smoke have not been documented.  A lot of young people, enamored with the electronic age, are frequent smokers of e-cigarettes which were thought to be less harmful than regular cigarettes of even safe.  Dr. Petrache’s (an Associate Editor of AJP-Lung) and her colleagues demonstrate that e-cigarette smoke damages not only epithelial cell (the first cells to come into contact with the injurious agents in smoke) but also endothelial cells causing decreased resistance of the endothelial barrier, increased permeability and lung inflammation. Although nicotine was responsible for the lion’ share of this injury (independent of its ability to generate reactive intermediates), even nicotine free e-smoke could cause significant injury due to the presence of other damaging compounds including acrolein.  The investigators proceeded in identifying the signaling events associated with an increase in endothelial permeability which are succinctly summarized in Figure 8 of their article (please read the article for the whole story).  Furthermore, they showed that enhancement of S1P1 (sphingosine-1 phosphate) lung levels prevented the deleterious effects of e-smoke most likely by reinforcing the tethering forces holding the endothelial cells together.

Clearly a lot more work has to be done to document the long term effects of e-cigarette smoke on the development of chronic lung and cardiovascular disease. However, it is safe to say that this article clearly demonstrates that e-cigarette smoke is not safe.  

AJP-Lung Featured Article

Alterations of lung microbiota in a mouse model of LPS-induced lung injury

Valeriy Poroyko , Fanyong Meng , Angelo Meliton , Taras Afonyushkin , Alexander Ulanov , Ekaterina Semenyuk , Omar Latif , Vera Tesic , Anna A. Birukova , Konstantin G. Birukov

American Journal of Physiology - Lung Cellular and Molecular Physiology Published 8 May 2015 Vol. no. , DOI: 10.1152/ajplung.00061.2014 

 

The origin of microorganisms that colonize the lung in the background of acute inflammation, and indeed, the acute respiratory distress syndrome (ARDS), is currently unclear. Much early work proposed that the origin of these colonizing bacteria was the introduction into the lung of external infectious agents that gave rise to the initiating conditions (such as bacterial pneumonia or aspiration-induced ARDS). In a recent issue of the Journal, Poroyko and colleagues hypothesized that the pathomechanisms that drive ARDS, including increased vascular permeability and the expression of cell-surface adhesion molecules, created an environment that was permissive for the growth of selected bacterial pathogens. Using a model of sterile acute lung injury in mice, where the administration of LPS drove lung injury and edema formation, the investigators demonstrated that this mode of lung injury created an ecological niche that promoted a “bloom” of previously dormant (but resident) microbial species. This phenomenon was attributed – at least in in part – to the influence of hypoxia on glucose metabolism, which led to abnormal lactate production and accumulation. This, together with other metabolic and permeability disturbances, created a niche that was optimal for bacterial growth. The most noteworthy conclusion of the investigators is that the morbid transformation of the lung microbiota could be attributed to the pre-existing innate pulmonary microbiota that were able to flourish in the environment of the acutely-inflamed lungs, rather than external infectious agents. Clearly, this study has its limitations, having been conducted in the setting of sterile lung inflammation. No doubt, future work will follow, which might address the development of septic lung injury in other contexts, such as (sterile) acid aspiration or saline lavage; or more directly clinically relevant approaches, such as caecal ligation and puncture. We look forward to seeing the results of these investigations in the pages of the Journal in the future, which will contribute much to our understanding of the basis of bacterial colonization of the lung in the background of an acute insult.

 

Commentary by Dr. Rory Morty, Deputy Editor AJP-Lung

AJP-Lung Featured Articles

Every three months, the Editor and Deputy Editors select five articles for inclusion in the FEATURED ARTICLE section of the AJP-Lung web page. (http://ajplung.physiology.org/)  These articles are likely to have a significant impact on their fields and they are the best demonstration of the excellence of AJP-Lung. They can be downloaded in their entirety even if a reader does not have a subscription to the journal.  A brief summary of one of these articles is provided by Dr. Rory Morty, Deputy Editor, of AJP-Lung.

Sadis Matalon, Editor in Chief. 

Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells

Artem Shkumatov , Michael Thompson , Kyoung M. Choi , Delphine Sicard , Kwanghyun Baek , Dong Hyun Kim , Daniel J. Tschumperlin , Y. S. Prakash , Hyunjoon Kong

American Journal of Physiology - Lung Cellular and Molecular Physiology Published 1 June 2015 Vol. 308 no. 11, L1125-L1135 DOI: 10.1152/ajplung.00154.2014

The extracellular matrix (ECM) has long been accredited with pathophysiological roles in the lung. A large volume of important work has addressed the ECM in lung disease, largely by examining the abundance or paucity of key ECM molecules, notably collagen and elastin, in the lungs of experimental animals or clinical subjects with lung disease. Little attention has been paid to how perturbations to ECM structure actually impact the physiological function of the ECM, particularly related to how the ECM structure may drive phenotypic changes in the behavior of lung cells that rest, or are in contact with, the underlying ECM. This is particularly important in tissues where disease processes results in major changes in the composition or distribution of the ECM. In a recent issue of the Journal, Shkumatov and colleagues report on how changes in the mechanical stiffness of a model matrix can influence the behavior of airway smooth muscle cells (ASMC).  In their study, the investigators cultured ASMC on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli. The remarkable observations were (i) that “softer” gels caused increased secretion of pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) by ASMC while in contrast; (ii) “harder” gels stimulated ASMC proliferation and reduced both VEGF secretion and histamine-induced calcium responses. These responses were correlated with the expression of components of the integrin system, namely integrin-beta1 and the integrin-linked kinase. Thus, the authors conclusively demonstrate that ASMC are very responsive to the mechanical stiffness of collagen-conjugated hydrogels, which are useful and elegant models of cell adhesion matrices that can be manipulated to alter the elastic modulus. These studies contribute enormously to an emerging body of work that has started to address how the properties (as opposed to the abundance) of the ECM may drive pathological (and indeed, normal physiological) processes. The authors are to be commended on a most interesting study, which will undoubtedly form the basis of further exciting studies that we hope to see published in the pages of the Journal in the future. 

Commentary by Dr. Rory Morty, Deputy Editor AJP-Lung

 

 

APSselect June 2015

Congratulations on our newest APSselect winners.

 Jamie Kuck, her mentor Mark Gillespie along with their colleagues recently published a very interesting paper in AJP-Lung, "Mitochondrial DNA damage-associated molecular patterns mediate a feed-forward cycle of bacteria-induced vascular injury in perfused rat lungs." To view all the "best" papers that the American Physiology Society published in June please visit http://apsselect.physiology.org/