Surfactant Protein-A Suppresses Eosinophil-Mediated Killing of Mycoplasma pneumoniae in Allergic Lungs

Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT) and SP-A−/− allergic mice challenged with the model antigen ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp) as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO), which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A−/− mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation and damage

B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease

Background: The role of B cells in allergic asthma remains undefined. One mechanism by which B cells clearly contribute to allergic disease is via the production of specific immunoglobulin, and especially IgE. Cognate interactions with specific T cells result in T cell help for B cells, resulting in differentiation and immunoglobulin secretion. Proximal to (and required for) T cell-dependent immunoglobulin production, however, is antigen presentation by B cells. While interaction with T cells clearly has implications for B cell function and differentiation, this study investigated the role that B cells have in shaping the T cell response during chronic allergic lung disease. Methodology/Principal Findings: In these studies, we used a clinically relevant mouse model of chronic allergic lung disease to study the role of B cells and B cell antigen presentation in this disease. In these studies we present several novel findings: 1) Lung B cells from chronically allergen challenged mice up-regulated MHC II and costimulatory molecules CD40, CD80 and CD86. 2) Using in vitro studies, B cells from the lungs of allergen challenged mice could present antigen to T cells, as assessed by T cell proliferation and the preferential production of Th2 cytokines. 3) Following chronic allergen challenge, the levels of Th2 cytokines IL-4 and IL-5 in the lungs and airways were significantly attenuated in B cell 2/2 mice, relative to controls. 4) B cell driven Th2 responses and mucus hyper secretion in the lungs were dependent upon MHC II expression by B cells. Conclusions/Significance: Collectively, these results provide evidence for antigen presentation as a novel mechanism b

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition?

Vođenje je najzahtjevnija menadžerska funkcija i kao takva plijeni pozornost znanstvene i stručne javnosti. Osnovni je zadatak vodstva pronaći i održavati ravnotežu između tri ključne varijable procesa vodstva, a to su: vođa, sljedbenici i situacija (okolina navedenih varijabli), a ono to može ukoliko vođa ima odgovarajuće sposobnosti, motivaciju i moć. Zbog toga je fenomen vođenja i uspješnih vođa uvijek zaokupljao pažnju ne samo znanstvene javnosti već i šire, što dovodi do pojave različitih teorija o vođenju i vođama i stilovima vođenja. Iako postoje brojna istraživanja koja dokazuju postojanje uzročno-posljedičnog odnosa između stila vođenja i ostvarenog poslovnog rezultata, još uvijek ne postoji konsensualno mišljenje o tome koji je stil vođenja najbolji za poslovni uspjeh tvrtke. S obzirom da je vještina vođenja vrlo važna u računovodstvenoj profesiji, nije iznenađujuće da računovodstvene organizacije i revizijske korporacije mnogo ulažu u obuku voditelja svojih revizora i budućih zaposlenika. U organima upravljanja i vođenja revizorskog poduzeća većinu moraju činiti osobe sa zvanjem ovlaštenog revizora. Revizori vođe trebaju posjedovati određene talente da bi uspjeli. Pored tehničkih vještina, oni moraju komunicirati sa svojim podređenima kako bi delegirali, vodili i prenosili znanje. Empirijsko istraživanje provedeno je intervjuom u dvoje malih revizorskih poduzeća prikazuje specifičnosti vodstva i vođenja u malim revizorskim društvima. Zbog važnosti vođenja kao najzahtjevnije menadžerske funkcije, pitanja u intervjuu odnosila su se na način i proces vođenja, koji uključuje motivaciju, komunikaciju i interpersonalne procese. Istraživanje je ukazalo da je procesu vođenja malih revizorskih poduzeća prevladava demokratski stil, no kod donošenja delikatnih odluka s većim rizikom, stil vođenja je autokratski. Također, vrlo je važna komunikacija i delegacija u procesu obavljanja revizije kako bi vođe uspješno vodili i prenosili znanje, te je važna usmjerenosti na zaposlenike, odnosno njihovu edukaciju i dodatno usavršavanje jer su oni ključan faktor kod obavljanju poslova revizije.Leadership is the most demanding managerial function and as such attracts the attention of the scientific and professional public. The basic task of leadership is to find and maintain a balance between the three key variables of the leadership process, namely: leader, followers and situation (environment of these variables), and this can be done if the leader has the appropriate abilities, motivation and power. Therefore, the phenomenon of leadership and successful leaders has always captured the attention not only of the scientific public but also wider, leading to the emergence of different theories about leadership and leaders and leadership styles. Although there is a number of studies proving the existence of a cause-and-effect relationship between leadership style and business performance, there is still no consensus opinion on which leadership style is best for a company’s business success. Given that leadership skills are very important in the accounting profession, it is not surprising that accounting organizations and audit corporations invest heavily in the training of their auditor leaders and future employees. In the management and governing bodies of an audit firm, the majority must be persons with the title of certified auditor. Leader auditors need to possess certain talents to succeed. In addition to technical skills, they must communicate with their subordinates to delegate, guide, and transfer knowledge. Empirical research was conducted by interviewing two small audit firms and shows the specifics of leadership and management in small audit firms. Because of the importance of leadership as the most demanding managerial function, the questions in the interview related to the manner and process of leadership, which includes motivation, communication, and interpersonal processes. Research has shown that the process of running small audit firms is dominated by a democratic style, but when making delicate decisions with a higher risk, the management style is autocratic. Also, communication and delegation is very important in the audit process in order for leaders to successfully lead and transfer knowledge, and it is important to focus on employees, i.e., their education and additional training because they are a key factor in performing audit work

Kinetic modeling of H-BEA and Fe-BEA as NH3-SCR catalysts - Effect of hydrothermal treatment

Kinetic modeling and flow reactor experiments were used to study the dynamic behavior of the active sites of H-BEA and Fe-BEA during NH3-SCR before and after hydrothermal aging of the catalysts. To capture transient changes it was crucial to describe NH3 and NO adsorption. For the H-BEA model the storage of ammonia was simplified to proceed on two zeolite sites representing weak and strong Br\uf8nsted acid sites, while NO only is adsorbed on Br\uf8nsted acid sites. Furthermore, the oxidation of NH3 and NO, and theNH3-SCR reaction are assumed to proceed over the Br\uf8nsted acid sites. To model Fe-BEA, monomeric and dimeric iron, and iron oxide particles represent sites of three different types of iron species. Ammonia and NO adsorb on monomeric iron which is assumed to be the governing site for low temperature SCR. Dimeric iron species provide the activity for high temperature SCR and NH3-oxidation. Furthermore, iron particles, Fe2O3, are not active for NH3-SCR but for oxidation of NO. A spillover mechanism of ammonia adsorbed on Br\uf8nsted acid sites to monomeric iron sites is included in the model to simulate the inhibiting effect of NH3 during the SCR reaction. The spillover rate was found to be independent of the site density and dependsonly on the fraction of free sites, indicating that a constant number of Br\uf8nsted acid sites buffer each activeiron site, unaffected by the hydrothermal treatment. The model describes the experiments well for HBEA and Fe-BEA before and after hydrothermal treatment by decreasing the site density and keeping the kinetic parameters constant except the binding energy of ammonia to Br\uf8nsted sites, which was found to decrease with hydrothermal treatment. Finally, the model was validated in separate ammonia inhibiting experiments, not used in the fitting process of the kinetic parameters. The aging model describes the validation experiments well

Kinetic modeling of H-BEA and Fe-BEA as NH₃-SCR catalysts - Effect of hydrothermal treatment

Kinetic modeling and flow reactor experiments were used to study the dynamic behavior of the active sites of H-BEA and Fe-BEA during NH3-SCR before and after hydrothermal aging of the catalysts. To capture transient changes it was crucial to describe NH3 and NO adsorption. For the H-BEA model the storage of ammonia was simplified to proceed on two zeolite sites representing weak and strong Brønsted acid sites, while NO only is adsorbed on Brønsted acid sites. Furthermore, the oxidation of NH3 and NO, and the NH3-SCR reaction are assumed to proceed over the Brønsted acid sites. To model Fe-BEA, monomeric and dimeric iron, and iron oxide particles represent sites of three different types of iron species. Ammonia and NO adsorb on monomeric iron which is assumed to be the governing site for low temperature SCR. Dimeric iron species provide the activity for high temperature SCR and NH3-oxidation. Furthermore, iron particles, Fe2O3, are not active for NH3-SCR but for oxidation of NO. A spillover mechanism of ammonia adsorbed on Brønsted acid sites to monomeric iron sites is included in the model to simulate the inhibiting effect of NH3 during the SCR reaction. The spillover rate was found to be independent of the site density and depends only on the fraction of free sites, indicating that a constant number of Brønsted acid sites buffer each active iron site, unaffected by the hydrothermal treatment. The model describes the experiments well for HBEA and Fe-BEA before and after hydrothermal treatment by decreasing the site density and keeping the kinetic parameters constant except the binding energy of ammonia to Brønsted sites, which was found to decrease with hydrothermal treatment. Finally, the model was validated in separate ammonia inhibiting experiments, not used in the fitting process of the kinetic parameters. The aging model describes the validation experiments well

Influence of hydrothermal ageing on NH3-SCR over Fe-BEA -Inhibition of NH3-SCR by ammonia

The decay in ammonia adsorption capacity and the amount of active iron sites are important to consider in order to understand the deactivation processes of Fe-BEA as NH3-SCR catalyst. NH3 and NO storage capacity experiments together with kinetic modeling have been used to evaluate ammonia inhibition during NH3-SCR before and after hydrothermal treatment of H-BEA and Fe-BEA. The kinetic model shows that at least four types of acid sites for H-BEA and one additional site for Fe-BEA are required to predict the NH3 desorption well. NH3-TPD experiments together with simulations show that the strongest adsorption sites are the sites that are most affected by the hydrothermal treatment. For H-BEA a clear correlation between the ammonia storage capacity and the improved NOX conversion after NH3 cut-off during NH3-SCR is observed. However, Fe-BEA show an inhibiting effect of ammonia after NH3 cut-off but no significant difference (i.e. increased NOX conversion time) between fresh and aged samples can be observed, indicating that the inhibiting effect is unaffected by the hydrothermal treatment