Background-Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways.
Background
Eosinophils and lymphocytes are pathogenically important in allergic inflammation and sensitive to Fas-mediated apoptosis. Fas Ligand (FasL) activity therefore should play a role in regulating the allergic immune response. We aimed to characterize the role of FasL expression in airway eosinophilia in Aspergillus fumigatus (Af)-induced sensitization, and to determine if FasL neutralization alters the inflammatory response.
Methods
Sensitized Balb/c mice were sacrificed before (Day 0) and 1, 7 and 10 days after a single intranasal challenge with Af. Animals received either neutralizing antibody to FasL (clone MFL4) or irrelevant hamster IgG via intraperitoneal injection on Days -1 and 5. FasL expression, BAL and tissue inflammatory cell and cytokine profile, and apoptosis were assessed.
Results
Post challenge FasL gene expression in BAL cells and TUNEL positivity in the airways coincided with the height of inflammatory cell influx on Day 1 while soluble FasL protein was released on Day 7, preceding resolution of the inflammatory changes. Although eosinophil numbers showed a negative correlation with soluble FasL levels in the airways, MBP+ eosinophils remained TUNEL negative in the submucosal tissue, throughout the 10-day period after Af challenge. Systemic FasL neutralization significantly enhanced BAL and tissue eosinophil counts. This effect was associated with increased activation of T cells and release of IL-5, IL-9 and GM-CSF in the BAL fluid of mice indicating an involvement of pro-eosinophilic survival pathways.
Conclusions
FasL activity may play an active role in resolving eosinophilic inflammation through regulating T cells and pro-eosinophilic cytokine release during the allergic airway response.
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