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Purpose Transport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion. Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT). Methods Pigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-[gamma]-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-[gamma]-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT. Results Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-[gamma] differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-[gamma] treatment reduces nasal colonization with S. pneumoniae. Conclusion Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-[gamma]-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR., Author(s): Alexander Pausder [sup.1] [sup.2] [sup.3], Jennifer Fricke [sup.4] [sup.9], Klaus Schughart [sup.4] [sup.5] [sup.6], Jens Schreiber [sup.7], Till Strowig [sup.8], Dunja Bruder [sup.1] [sup.2], Julia D. Boehme [sup.1] [sup.2] [...]

Background: COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD. Methods: To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis. Results: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction. Conclusions: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients. [ABSTRACT FROM AUTHOR]