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Rationale: There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on "self" proteins. Objectives: To determine the presence of autoantibodies to carbonylmodified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins. Methods: Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescenceactivated cell sorter. Measurements and Main Results: Antibody titer against carbonylmodified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonylmodified protein.Conclusions: Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD.Keywords: COPD; autoimmunity; oxidative stress; carbonyl Chronic obstructive pulmonary disease (COPD) is currently a leading cause of morbidity and mortality worldwide (1), with the main cause being long-term cigarette smoking in the western world (1, 2). Inflammation and remodeling of the small airways are major determinants for the progression and severity of COPD, as defined by the decline in FEV 1 (3). Accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells, such as CD4 1 cells, CD8 1 cells, B cells, macrophages, and neutrophils, and the formation of lymphoid follicles are all features of the observed inflammation that correlate with the severity of COPD (3, 4).Previous studies have suggested that autoimmune mechanisms may contribute to the pathogenesis of COPD. Serum autoantibodies against elastin (5) and bronchial epithelial cells along with corresponding IgG and complement (C3) deposition (6) have been observed in COPD lung. It has therefore been proposed that cigarette smoke-derived antigens may be responsible for driving this disease process in COPD (...

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Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20nm and 110nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.

For excited nucleon states N * of arbitrary spin coupling to nucleon (N) and meson (M), we propose a Lorentz covariant orbital-spin (L-S) scheme for the effective N * N M couplings. To be used for the partial wave analysis of various N * production and decay processes, it combines merits of two conventional schemes, i.e., covariant effective Lagrangian approach and multipole analysis with amplitudes expanded according to angular momentum L. As examples, explicit formulae are given for N * → N π, N * → N ω and ψ → N * N processes which are under current experimental studies.