Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered

Pulsed Electron-Electron Double Resonance (PELDOR) and Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy in Bioanalysis

Electron Paramagnetic Resonance (EPR) has a long history with the first spectrum being reported in 1945 (Zavoisky 1945) and is adopted widely, in its original continuous wave (CW) form, as a tool for the analysis of both biological systems and materials bearing unpaired electrons. The related technique of “Nuclear Magnetic Resonance” (NMR) developed rapidly thanks to the technological advances that enabled the use of pulsed radiofrequency and Fourier Transformation (FT). In EPR, the challenges posed by needing to generate short and very powerful microwave pulses and the fast relaxation times, of the electron spin, led to a much slower adaptation of pulsed excitation schemes. Nevertheless, early experiments using an NMR spectrometer with a greatly reduced magnetic field had shown the feasibility of pulse EPR (Blume 1958). It was not until the availability of commercial systems in the 1980s that this technique began to be applied more widely outside laboratories focused on the development of instrumentation. Over the last decades the application of pulse EPR has seen a very wide variety of systems studied from biological systems to those of materials science. This development was paralleled by a constant innovation in EPR instrumentation and methodology. Recent success in using arbitrary waveform generators (AWGs) and the commercial implementation and user uptake indicates that EPR is just entering a new era with tremendous opportunities offered by bespoke excitation schemes.Postprin