Our results point to a deficient PGE(2) production under proinflammatory conditions in asthmatic airways. This could weaken local defensive mechanisms and promote cysteinyl leukotriene overproduction.
Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.
In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways.Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC.Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean¡SD maximal fall in FEV1 27¡13%; associated increase in adenosine 110¡76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients.In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.
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