Infrared Behaviour of Systems With Goldstone Bosons

We develop various complementary concepts and techniques for handling quantum fluctuations of Goldstone bosons.We emphasise that one of the consequences of the masslessness of Goldstone bosons is that the longitudinal fluctuations also have a diverging susceptibility characterised by an anomalous dimension $(d-2)$ in space-time dimensions $2<d<4$.In $d=4$ these fluctuations diverge logarithmically in the infrared region.We show the generality of this phenomenon by providing three arguments based on i). Renormalization group flows, ii). Ward identities, and iii). Schwinger-Dyson equations.We obtain an explicit form for the generating functional of one-particle irreducible vertices of the O(N) (non)--linear $\sigma$--models in the leading 1/N approximation.We show that this incorporates all infrared behaviour correctly both in linear and non-linear $\sigma$-- models. Our techniques provide an alternative to chiral perturbation theory.Some consequences are discussed briefly.Comment: 28 pages,2 Figs, a new section on some universal features of multipion processes has been adde

The effects of nitric oxide of human rhinovirus-induced cxcl10 production in airway epithelial cells

Bibliography: p. 150-17

Surfactant and bronchial response

Bibliography: p. 122-132A variety of clinical and experimental evidence indicates that surfactant may be important in the pathogenesis and treatment of asthma. The purpose of this study was to determine the effect of pulmonary surfactant and/or its components on precontracted rat bronchi. Left and right first generation bronchial tissues from male Sprague-Dawley rats were used in the studies done in vitro. Precontracted tissues were exposed to three kinds of surfactant: natural rat surfactant (NRS), bovine lipid extract surfactant (BLES), and Survanta. Surfactant was shown to relax rat bronchi in a concentration-dependent manner. The mechanism of surfactant-induced relaxation was determined. The surfactant relaxation response was inhibited when tissues were devoid of epithelium or when they were treated with indomethacin. N-co-nitro-L-arginine methyl ester (L-NAME) did not affect the surfactant-induced relaxation. Surfactant lipids, unsaturated phosphatidyicholine (uPC), dipalmitoylphosphatidylcholine (DPPC), and phosphatidyiglycerol (PG), and surfactant-specific protein A (SP-A) also showed a relaxant effect whereas non-surfactant lipids and proteins did not. We conclude that surfactant is an airway smooth muscle relaxant. The effect is specific and is dependent on the presence of epithelium and release of prostanoids, but is not dependent on the nitric oxide (NO) pathway

Selective transcriptional down-regulation of human rhinovirus-induced production of CXCL10 from airway epithelial cells via the MEK1 pathway.

Human rhinovirus (HRV) infections can trigger exacerbations of lower airway diseases. Infection of airway epithelial cells induces production of a number of proinflammatory chemokines that may exacerbate airway inflammation, including CXCL10, a chemoattractant for type 1 lymphocytes and NK cells. Primary human bronchial epithelial cells and the BEAS-2B human bronchial epithelial cell line were used to examine the role of MAPK pathways in HRV-16-induced production of CXCL10. Surprisingly, PD98059 and U0126, two inhibitors of the MEK1/2-ERK MAPK pathway, significantly enhanced HRV-16-induced CXCL10 mRNA and protein. This enhancement was not seen with IFN-beta-induced production of CXCL10. Studies using small interfering RNA revealed that knockdown of MEK1, but not MEK2, was associated with enhanced HRV-induced CXCL10 production. Promoter construct studies revealed that PD98059 and U0126 enhanced HRV-16-induced transcriptional activation of CXCL10. HRV-16-induced promoter activation was regulated by two NF-kappaB binding sites, kappaB1 and kappaB2, and by an IFN-stimulated response element. Inhibitors of the MEK1/2-ERK pathway did not alter HRV-16-induced activation of tandem repeat kappaB1 or kappaB2 constructs, nor did they alter HRV-16-induced nuclear translocation/binding of NF-kappaB to either kappaB1 or kappaB2 recognition sequences. Furthermore, PD98059 and U0126 did not alter phosphorylation or degradation of IkappaBalpha. In contrast, inhibitors of the MEK1/2-ERK pathway, and small interfering RNA knockdown of MEK1, enhanced nuclear translocation/binding of IFN regulatory factor (IRF)-1 to the IFN-stimulated response element recognition sequence in HRV-16 infected cells. We conclude that activation of MEK1 selectively down-regulates HRV-16-induced expression of CXCL10 via modulation of IRF-1 interactions with the gene promoter in human airway epithelial cells

Nitric oxide inhibits human rhinovirus-induced transcriptional activation of CXCL10 in airway epithelial cells

BACKGROUND Human rhinovirus (HRV) infections trigger exacerbations of asthma and chronic obstructive pulmonary disease. Nitric oxide (NO) inhibits HRV replication in human airway epithelial cells and suppresses HRV-induced epithelial production of several cytokines and chemokines. OBJECTIVE We sought to delineate the mechanisms by which NO inhibits HRV-induced epithelial production of CXCL10, a chemoattractant for type 1 T cells and natural killer cells. METHODS Primary human bronchial epithelial cells or cells of the BEAS-2B human bronchial epithelial cell line were exposed to HRV-16 in the presence or absence of the NO donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPA NONOate). A cGMP analogue and an inhibitor of soluble guanylyl cyclase were used to examine the role of the cyclic guanosine monophosphate (cGMP) pathway in the actions of NO. BEAS-2B cells were transfected with CXCL10 promoter-luciferase constructs and the effects of PAPA NONOate were examined to study mechanisms of transcriptional regulation. Electrophoretic mobility shift assays were also used. RESULTS PAPA NONOate inhibited HRV-16-induced increases in CXCL10 mRNA and protein. Inhibition of CXCL10 production occurred through a cGMP-independent pathway. PAPA NONOate inhibited HRV-16-induced CXCL10 transcription by blocking nuclear translocation, binding, or both of both nuclear factor kappaB and IFN response factors (IRFs) to their respective recognition elements in the CXCL10 promoter. CONCLUSIONS NO inhibits HRV-16-induced production of CXCL10 by inhibiting viral activation of nuclear factor kappaB and of IRFs, including IRF-1, through a cGMP-independent pathway. The broad-ranging inhibition of HRV-induced epithelial cytokine and chemokine production by NO suggests a potential therapeutic utility of NO donors in viral exacerbations of asthma and chronic obstructive pulmonary disease

Analysis of Endogenous Particles in Exhaled Air

Exhaled air contains non-volatile particulate material from the respiratory tract. The precise location in which exhaled particles are formed is unknown, and details on their chemical content are scarce. The aim of this work was to chemically characterize and to study the mechanisms of formation of endogenous particles in exhaled air. A new instrument for counting and sampling particles in exhaled air by impaction was developed, as a part of this thesis, at the Department of Public Health and Community Medicine, Occupational and Environmental Medicine in collaboration with the Department of Chemistry, Atmospheric Science at the University of Gothenburg. In the first instance, exhaled particles were analyzed using time-of-flight secondary ion mass spectrometry (TOF-SIMS), which is a very sensitive technique for surface analysis. This method was also used to compare the composition of particles in exhaled air from subjects with asthma to that in healthy controls. Second, a method for the quantitative determination of glutathione was developed and applied in the analysis of exhaled particles and exhaled breath condensate. In parallel to chemical analysis, the hypothesis that particles are formed during the reopening of closed airways was tested by measuring particle number concentrations in the air exhaled by healthy volunteers performing different breathing maneuvers. This is the first study involving chemical analysis of particles in exhaled air. TOF-SIMS analysis revealed that exhaled particles contain several phospholipids (phosphatidylcholine, phosphatidylglycerol and phosphatidylinositol). These lipids are characteristic of the pulmonary surfactant which is present in the respiratory tract lining fluid (RTLF) that covers the epithelium in the alveoli and the airways. Using this method, it was found that the TOF-SIMS spectra of the particles exhaled by healthy subjects differed from those of the particles exhaled by subjects with asthma. These differences were attributed to differences in the abundance of phosphatidylcholine and phosphatidylglycerol between the two groups. By using the newly-developed method for glutathione analysis, it was possible to demonstrate the presence of glutathione in exhaled particles for the first time. The method was used to compare glutathione levels in exhaled particles to those in exhaled breath condensate; it was found that analysis of particles was more revealing in terms of the levels of glutathione in exhaled air. Studies of particle formation showed that deep exhalations to residual volume (RV) caused significantly higher concentrations of particles in the subsequent exhalation than did exhalations to functional residual capacity (FRC).This supports the theory that film rupture during airway reopening after airway closure is an important mechanism of particle formation. The results of these studies show that particles in exhaled air can be sampled by impaction, that surfactant phospholipids and glutathione are part of their chemical composition, and that they are largely formed in the peripheral airways, where airway closure takes place