Alveolar epithelial and endothelial cell apoptosis in emphysema: What we know and what we need to know

Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space. However, mechanisms involved in its development are not fully understood. Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated. Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research. Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema. Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema. This review also includes some reflections and suggestions on the research to come

The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis

Objectives Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice

Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema-1

<p><b>Copyright information:</b></p><p>Taken from "Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema"</p><p>http://respiratory-research.com/content/8/1/62</p><p>Respiratory Research 2007;8(1):62-62.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2018693.</p><p></p>d cell count. B) PBMC were isolated from each subjects, double labelled with fluorochrome-conjugated antibodies (CD3/CD4 and CD3/CD8), and analysed by flow cytometry. For each subject, CD4/CD8 ratio was obtained by dividing the %CD3/CD4cells by the %CD3/CD8cells. Columns represent mean ± SEM. *p = 0.02. Normal non-smokers (white), normal smokers (black), and emphysematous smokers (grey)

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema-3

<p><b>Copyright information:</b></p><p>Taken from "Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema"</p><p>http://respiratory-research.com/content/8/1/62</p><p>Respiratory Research 2007;8(1):62-62.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2018693.</p><p></p>expression of granzyme B, perforin, and FasL was assessed by real-time PCR, using 18S rRNA as housekeeping gene and compared using 2method. Columns represent mean ± SEM. *p = 0.02; **p = 0.05. Normal non-smokers (white), normal smokers (black), and emphysematous smokers (grey)

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema-2

<p><b>Copyright information:</b></p><p>Taken from "Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema"</p><p>http://respiratory-research.com/content/8/1/62</p><p>Respiratory Research 2007;8(1):62-62.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2018693.</p><p></p>ted anti-CD56, CD4, CD8, or CD3, permeabilized, then labelled with fluorochrome-conjugated anti- A) granzyme B or B) perforin and analysed by flow cytometry. Columns represent mean ± SEM. Normal non-smokers (white), normal smokers (black), and emphysematous smokers (grey)

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema-0

<p><b>Copyright information:</b></p><p>Taken from "Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema"</p><p>http://respiratory-research.com/content/8/1/62</p><p>Respiratory Research 2007;8(1):62-62.</p><p>Published online 6 Sep 2007</p><p>PMCID:PMC2018693.</p><p></p>RP levels were quantified by high sensitivity nephelometry. Columns represent mean ± SEM. *p = 0.002; **p = 0.0003. Normal non-smokers (white), normal smokers (black), and emphysematous smokers (grey)