Purinergic P2x7 Receptor: Pathophysiological Role in Alveolar Functions

Veterinary Biomedical Science

Manufacture of the Futuristic Castable Type of Screening Smoke Composition

The present trend abroad is to replace conventional smoke compositions with castable type of smoke compositions because of superior performance of the latter over the former. The technology of castable screening smokes has been recently developed for the first time in India by the Explosives Research & Development Laboratory, Pune. This paper discusses the various advantages in large scale manufacture of castable type of screening smoke composition. A comparison is also made with the conventional method of manufacture of screening smoke composition currently followed

MicroRNA-206 regulates surfactant secretion by targeting VAMP-2

AbstractLung surfactant secretion is a highly regulated process. Our previous studies have shown that VAMP-2 is essential for surfactant secretion. In the present study we investigated the role of miR-206 in surfactant secretion through VAMP-2. VAMP-2 was confirmed to be a target of miR-206 by 3′-untranslational region (3′-UTR) luciferase assay. Mutations in the predicated miR-206 binding sites reduced the binding of miR-206 to the 3′-UTR of VAMP-2. miR-206 decreased the expression of VAMP-2 protein and decreased the lung surfactant secretion in alveolar type II cells. In conclusion, miR-206 regulates lung surfactant secretion by limiting the availability of VAMP-2 protein

Vacuolar ATPase Regulates Surfactant Secretion in Rat Alveolar Type II Cells by Modulating Lamellar Body Calcium

Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase) dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1), an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca2+ chelator, BAPTA-AM, the protein kinase C (PKC) inhibitor, staurosporine, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII), KN-62. Baf A1 induced Ca2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion

Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma

Dendritic cells (DCs) are highly specialized in antigen presentation and play a pivotal role in the initiation, progression, and perpetuation of adaptive immune responses. Emerging immune pathways are being recognized increasingly for DCs and their subsets that differentially regulate T lymphocyte function based on the type and interactions with the antigen. However, these interactions not only alter the signaling process and DC function but also render metabolic plasticity. The current review focuses on the metabolic cues of DCs that coordinate DC activation and differentiation and discuss whether targeting these fundamental cellular processes have implications to control airway inflammation and adaptive immunity. Therefore, strategies using metabolism-based therapeutic manipulation of DC functions could be developed into novel treatments for airway inflammation and asthma

From bedside to bench to clinic trials: identifying new treatments for severe asthma

Asthmatics with a severe form of the disease are frequently refractory to standard medications such as inhaled corticosteroids, underlining the need for new treatments to prevent the occurrence of potentially life-threatening episodes. A major obstacle in the development of new treatments for severe asthma is the heterogeneous pathogenesis of the disease, which involves multiple mechanisms and cell types. Furthermore, new therapies might need to be targeted to subgroups of patients whose disease pathogenesis is mediated by a specific pathway. One approach to solving the challenge of developing new treatments for severe asthma is to use experimental mouse models of asthma to address clinically relevant questions regarding disease pathogenesis. The mechanistic insights gained from mouse studies can be translated back to the clinic as potential treatment approaches that require evaluation in clinical trials to validate their effectiveness and safety in human subjects. Here, we will review how mouse models have advanced our understanding of severe asthma pathogenesis. Mouse studies have helped us to uncover the underlying inflammatory mechanisms (mediated by multiple immune cell types that produce Th1, Th2 or Th17 cytokines) and non-inflammatory pathways, in addition to shedding light on asthma that is associated with obesity or steroid unresponsiveness. We propose that the strategy of using mouse models to address clinically relevant questions remains an attractive and productive research approach for identifying mechanistic pathways that can be developed into novel treatments for severe asthma

Poly[diaquo(1,10-phenanthroline-κ 2 N 1 :N 10 )(μ 2 -sulphato-κ 2 O:O′)copper( ii )]: hydrothermal synthesis, crystal structure and magnetic properties

International audienceOf late, hydrothermal synthesis has gained much interest in the synthesis of metal–organic hybrid complexes with fascinating architectures and topologies. Product formation in such syntheses often depends on the nature of solvents, counter ions, pH and the ligand geometry. Copper-1,10-phenanthroline, or similar ligand systems, have been very popular in supramolecular chemistry over the years. Hence, a new metal–organic hybrid complex poly[diaquo(1,10-phenanthroline-κ2N1:N10)(μ2-sulphato-κ2O:O′)copper(II)], i.e., [Cu(C12H8N2)(H2O)2(μ-SO4)]n was synthesized by the hydrothermal method. Physico-chemical characterization of the complex was done using FTIR spectroscopy, single crystal X-ray diffraction, TGA, EPR, SQUID and FESEM. Single crystal X-ray diffraction studies revealed it to be three-dimensional with space group I2/c (monoclinic) and the unit cell dimensions are a = 7.0081 (3), b = 13.8198 (7) and c = 14.2897 (8) Å; the axial angles are α = 90°, β = 99.282 (5)° and γ = 90°. It features chains in which two successive pairs of Cu(II) ions are connected by SO4 bridges and Cu(II) ions, each coordinated to two H2O molecules and two N-atoms of 1,10-phenanthroline, and the title complex has a distorted octahedral geometry. The alternating polymeric chains are connected through extensive hydrogen bonds between two O-atoms of SO4 bridges from one chain and H atoms of the two coordinated H2O molecules of another chain in the three dimensional architecture. Alternating chains are shifted with respected to each other leading to the formation of zigzag channels within the crystal structure. EPR and SQUID studies revealed the paramagnetic nature of the complex