Lab Report

In chronic obstructive pulmonary disease (COPD), the airways and tissues of the lungs gradually become damaged over time, causing

As you already know, Chronic Obstructive Pulmonary Disease (COPD), manifests itself when the passageway of air to the lungs is severely obstructed, thus preventing sufficient flow of oxygen into the bloodstream.1 The pathophysiology of COPD is a complex process that is the result of multiple airway diseases that simultaneously contribute to the impairment of airflow in the lungs.1 Specifically, the overlapping outcome of chronic bronchitis and emphysema is the pathogenesis of COPD.1 The risk factor for the COPD is influenced by the individual’s genetics, age, gender, exposure to air pollution, socioeconomic status, and the use of tobacco products.1 The use of tobacco products can increase the development of COPD.1 However, individuals that don’t smoke can also attain COPD.1 Therefore, COPD is not exclusive to individuals that smoke on a daily basis.1 In fact, genetics and the natural aging process plays a part in the development of pulmonary issues.1 For example, it has been proven that a deficiency in the alpha -1 antitrypsin gene is correlated with the development of COPD.1 The natural deterioration of lung tissue, coupled with the long term exposure to environmental elements, explains why the risk of attaining COPD increases as one progresses to the latter stages of their lives.1 In a healthy individual, goblet cells secrete about one liter of mucous that provides a moist surface over the lungs, trachea, and esophagus.1 The cilia on the pseuodocolumnar epithelial cells continuously sweep the mucus in the lungs in an upward motion.1 The cilia sweeps the mucosal trapped debris up, and removes pathogens and other foreign particles out the pulmonary tissue.1 In individuals with COPD, the pathogenesis of the disease creates structural modifications of the lung tissue, which result in deformed and nonfunctioning cilia.2 The lack of functioning cilia leads to the buildup of mucous, pathogens, and subsequent respiratory infections.2 Furthermore, the body tries to combat

Briefly, Mice lung tissue will be isolated and cut into small pieces with razor blade and process in digestion buffer (1 mg/ml collagenase D, 0.1 mg/ml DNase; Roche, Indianapolis, IN) for 30 min. at 37℃. The samples will be passed through 100 μm and 40 μm strainer serially. After counting cells, alveolar macrophage specific and activation antibodies will be conjugated. CD11c+CD64+ cells will be gated and the activation markers (CD11b, CD40, CD80, CD86, MHC ll) will be analyzed. Alveolar macrophage gene expression will be evaluated after isolating the cells by BD FACS Aria (BD Bioscience, San Jose,

In both large and small airways in this CAL group, staining for S-100A4 and vimentin was focused in the deeper basal cell layer of the epithelium located in close proximity to the Rbm. This may highlight the likelihood of these cells being especially involved in undergoing transition to a mesenchymal phenotype. Similar positive staining of cells contained in the clefts of the disrupted Rbm further strengthens this concept of transition and migration of these basal cells. We have previously shown that the Rbm cells are not immune or inflammatory cells, and that they do strongly express matrix

Asthma and COPD (chronic obstructive pulmonary disease) are the most common inflammatory diseases of the lung. Asthma is an inflammatory disease of the respiratory tract and characterized by bronchial hyper-reactivity, airway constriction, loss of breath, wheezing and mucus production in the lung. In the world, the number of individuals suffering from asthma is increasing at an alarming rate. About 18.7 million adults and 6.8 million of children in the United States suffer from asthma as reported by CDC (Asthma, n.d.). Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that leads to obstructed airflow from the lungs. Inflammatory response to cigarette smoke is a major cause for the development of chronic obstructive

The pathology of asthmatic symptoms is quite complex, and includes the effects of mast cells, eusinophils, T cell lymphocytes, mactrophages, neutrophila, and epithelial cells, which collectively lead to inflammation. Pathologic qualities of asthma include goblet cell hyperplasia leading to mucus overproduction, basement membrane thickening with subepithelial fibrosis, desquamation of the airway epithelium, bronchial smooth muscle hyperplasia, and cellular infiltration with lymphocytes, neutrophils, and eosinophils. Airflow obstruction is caused by the smooth muscle constriction around airways, leading to wheezing, coughing, and chest tightness. Exposure to allergens, irritants (eg smoke), and viral infections can also

Airway inflammation and tissue injury with subsequent abnormal repair may lead to structural changes in the airway of asthmatic subjects that defined as airway remodeling. Airway remodeling contributes to irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity and impaired pulmonary function. [5] Reversal of remodeling gain therapeutic importance, and mechanisms responsible for airway remodeling has become an important target for asthma treatment (Shifren,

In 2009, 7.1 million children in the United States were diagnosed with asthma (Grossman & Mattson Porth, 2014). Asthma is a chronic airway disorder resulting in episodes of airway inflammation, airway obstruction, airway remodeling, and bronchial hyperresponsiveness. The deregulated inflammation leads to recurrent chest wheezing, cough, and shortness of breath. Asthma can be broken into several phenotypes, based on clinical and functional characteristics of the disease. Clinical manifestations may be from mild to severe and in some individuals deadly (Chesne, Braza, Mahay, Brouard, Aronica, & Magnan, 2014).

Also in mice model of PPE and LPS induced COPD were observed airway remodeling, lung inflammation, goblet cell hyperplasia, alveolar enlargement [59]. In other studies, similarly, emphysematous destruction, parenchymal inflammation, mucus hyper secretion and airway remodeling in murine model of COPD were reported after cigarette smoke exposure [40, 97-101]. In addition, significant increase in wall thickness and airspace size observed after smoke exposure in mice [102,

The early asthmatic response is the initial exposure of the antigen to the bronchial mucosa (McCance, 2014). Dendritic cells present the antigen to CD4+ T cells which become Th2 cells which release cytokines. The Cytokines IL-4, IL-5, IL-8, IL-13, IL-17, and IL-22 are released. Antigen specific IgE production is stimulated by IL-4. Il-5 stimulates the proliferation of eosinophils which cause tissue injury and toxic neuropeptides which contribute to hyperresponsiveness, fibroblast proliferation, airway scarring, and epithelial injury. Inflammatory response is exaggerated by neutrophil activation by IL-8. IL-13 reduces mucociliary clearance, enhances fibroblast secretion and helps bronchoconstriction and airway remodeling. Neutrophilic inflammation is increased by IL-17 and IL-22 stimulates airway epithelial cells which stimulate further adaptive immune responses. Degranulation of the mast cells, caused by the Fc portion of IgE binding to receptors on the surface of mast cells, releases inflammatory mediators which cause vasodilation, increased capillary permeability, mucosal edema, bronchial smooth muscle contraction, and mucous secretion of the goblet cells and narrowing of the airways (McCance, 2014).

Histamine, tumour necrosis factor α, and newly generated lipid mediators such as leukotriene C4 and prostaglandin D2, participate in the influx of inflammatory cells-e.g., eosinophils, CD4+ T lymphocytes, and basophils-by stimulation of expression of adhesion molecules on endothelial cells. Influx of these cells characterises the late allergic response, with nasal obstruction as the main presenting symptom. Allergen-specific IgE and eosinophilic nasal inflammation are distinctive for allergic rhinitis which these features differentiate allergic from other forms of the disorder. Further, allergic rhinitis has a systemic nature. One example is up regulation of eosinophils in bronchial mucosa after nasal allergen challenge, and vice

The overall goal of my laboratory is to study the mechanism of alveolar type II cell injury in emphysema. The mechanism of this disease pathophysiology is not well known. There is a very limited therapeutic strategy against emphysema. This disease is a primary indication for lung transplantation. However, this also leads to high mortality related to cardiovascular problems. Therefore, our projects are focused on identification of potential novel therapeutic targets and have translational and clinical implications. To our knowledge, my laboratory is the first to isolate primary alveolar type II cells from excess tissue obtained from patients with emphysema. We also obtain tissue from control organ donors whose lungs were not suitable for transplantation

Currently, soluble mediators are used as indirect markers of airway inflammation. Among them endothelin-1, which is produced by the bronchial epithelium, alveolar macrophage, and pulmonary endothelium, may stimulate mucus secretion, promote airway edema, increase vascular and airway smooth muscle proliferation, and up-regulate production of various cytokines [123]. Endothelin-1 has been proposed as one possible mediator responsible for increased airflow obstruction via bronchospasm induction, which is higher in the sputum of patients with stable COPD [124] as compared with healthy

It seems that innate and adaptive immune system cooperate with each other to manifest respiratory symptoms in COPD patients. Actually, irritant substances such as inhaled cigarette smoke induce and activate macrophages, neutrophils, natural killer cells, which belong to the innate immune system as well as epithelial cells in lungs. Activation of these cells causes release of substances called chemotactic cells, for instance, C‑chemokine ligand 2 (CCL2) that leads to attracting inflammatory cells such as monocytes. In addition, these macrophages and epithelial cells release multiple chemokines, including fibroblast growth factor (FGF) that causes proliferation of fibroblast and as a result, remodeling of airways. Furthermore, activated dendritic cells stimulate adaptive immune system that consists of different kinds of cells such as cytotoxic CD8+ T cells, T helper CD4+T cells, and B-cell. Therefore, lymphoid follicles on chronic inflammation are formed due to the response of these types of adaptive immune cells.

The inhaled irritants cause accumulation of inflammatory cells such as (neutrophils, B cells, CD8+ T-lymphocytes and macrophages). When these cells activated , they initiate an inflammatory cascade that lead to release of inflammatory mediators such as[ tumour necrosis factor alpha , C-reactive protein , interferon gamma , MMP-9, interleukins (IL-1, IL-6, IL-8) and fibrinogen]. The inflammatory mediators enhance the inflammatory process , cause tissue damage and systemic effects. The chronic inflammation leads to structural changes in the lung which lead to restriction of the airflow.[13]