Heterogeneity of mononuclear phagocytes in interstitial lung diseases

Interstitial lung diseases are a heterogeneous group of illnesses with different pathogeneses. In interstitial lung diseases there often is an increased influx of cells from the peripheral blood (PB) to the interstitium and alveoli. Besides the increase in total cell numbers, often marked shifts in the cell populations occur. This thesis describes the immunophenotype of the cells involved in three types of interstitial lung diseases, namely sarcoidosis, idiopathic pulmonary fibrosis (IPF) and extrinsic allergic alveolitis (EM). Emphasis is put on monocytic cells and macrophages. The cell surface markers of monocytes and macrophages as well as the immunophenotype of cultured purified monocytes have been studied. In addition surface antigens of cells from PB and bronchoalveolar lavage (BAL) fluid have been studied in the forementioned interstitial lung disease

The System: Reimagining Richmond: Diversity at the University of Richmond

Research and Capstone projects for The System Building on the 2017 fall semester and insights from the trip to Los Angeles, student working groups will predict the future of a system or related issue for an audience of their peers, offering reflections on navigating that future. These projects might take the form of posters, video installations, original speculative fiction, or mixed media that will be incorporated into the atmosphere of a campus party, both to maximize the student audience, and to celebrate our determination for an exciting future.https://scholarship.richmond.edu/ssir-presentations-2018/1001/thumbnail.jp

Lung dendritic cells and host immunity to infection

The lung is a portal of entry for numerous microbial pathogens, against which evolution has created an adequate innate and adaptive immune response. Dendritic cells (DCs) are central to the integration of innate and specific immunity. These cells are located within the epithelium and interstitium of the lung where they are influenced by the innate immune system. Upon recognition and internalization of microbial antigens, DCs migrate to the draining lymph nodes of the lung to initiate the specific cellular and humoral immune response. By their capacity to integrate stimuli derived from the pathogen, the host and the environment, they are specialized to induce a protective immune response while at the same time avoiding damage to the host. It is becoming increasingly clear that dendritic cells are involved in the induction of immunity to viruses, bacteria, mycobacteria and fungi. Some pathogens subvert the function of dendritic cells to escape immune recognition. Not surprisingly, if dendritic cell function fails, the consequence for the host is immunodeficiency

Cyclic AMP enhancing drugs modulate eicosanoid release from human alveolar macrophages

The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), salbutamol and sodium nitroprusside was evaluated regarding PGE2 and LTB4 release and cAMP and cGMP level in human alveolar macrophages obtained from controls and COPD patients. Basal levels per five million control-respectively COPD alveolar macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE2 120 and 63 pg and LTB4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55–93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB4 release by salbutamol+IBMX the drugs hardly affected PGE2 and LTB4 release from control macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol largely reduced PGE2 release (63 vs 11 pg per 106 cells) but less efficiently increased LTB4. In both macrophage populations sodium nitroprusside (SNP) substantially increased (3–4 fold) cGMP level but did not affect eicosanoid production. Present results indicate that drugs which enhance cAMP level decrease PGE2 release from COPD macrophages and stimulate the release of LTB4 a chemotactic mediator involved in bronchial inflammatory reactions

Effect of an inhaled glucocorticoid on reactive oxygen species production by bronchoalveolar lavage cells from smoking COPD patients

Oxidative stress in the lung is important in the pathogenesis of COPD. Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species (ROS). We investigated the effect of Fluticasone propionate (FP) on the ROS production capabilities of pulmonary cells. Bronchoalveolar lavage (BAL) was performed in smoking COPD patients, before and after a six month, placebo-controlled treatment with FP. BAL cells were stimulated with phorbol myristrate acetate (PMA) alone, and together with superoxide dismutase (SOD). From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production: Vmax. We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants. Paired results were obtained from 6 FP- and 9 placebo-treated patients. No significant change of Vmax was found in both patient groups. Also BAL cellularity was unchanged. Correlation analyses showed a significant (inverse) association of Vmax with the number of cigarettes smoked per day. We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients. Apparently, heavy smoking impaired the ability of alveolar macrophages to produce ROS, which was not further decreased by FP

Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease.

BACKGROUND: In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone. AIMS: To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo. METHODS: A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6). RESULTS: Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%). CONCLUSIONS: In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients

Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

Asthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose at 20% fall of baseline forced expiratory volume in 1 s (FEV1), but also a plateau (P) representing the maximal narrowing response in terms of percent change in FEV1 and reactivity as the steepest slope at 50% of P (%FEV1/doubling dose). In the baseline condition, the specific airway conductance (sGaw) may be considered closely related to airway lumen diameter. In 20 nonsmoking asthmatic patients, methacholine dose-response curves were obtained, and a sigmoid model fit yielded the BHR indexes. Immunohistochemistry with the monoclonal antibodies (EG1 and EG2) was used to recognize the total number of eosinophils and activated eosinophils, respectively. The number of activated eosinophils was significantly correlated to both P (r = 0.62; P < 0.05) and sGaw (r = -0.52; P < 0.05), whereas weaker and nonsignificant correlations were found for dose at 20% fall of baseline FEV1 and the total number of eosinophils. We conclude that the number of activated eosinophils can be considered a marker of the inflammation-induced decrease of airway lumen diameter as represented by the plateau index and sGaw