Resolution of Airway Eosinophilia is Associated with Upregulation of Fas Ligand (FasL) Expression After a Single Aspergillus fumigatus (Af) Challenge of Sensitized Mice

S.K. Sharma1, S. Kierstein2, A. Pitt3, F. Almeida3, J. Peterson1, X. Yang2, J. Zangrilli13, A. Haczku2

Author address: 

1 Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 2 Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 3 Division of Critical Care, Pulmonary, Allergic


RATIONALE: Eosinophils and T cells are intimately linked to the pathogenesis of allergic airway inflammation and both are susceptible to Fas mediated apoptosis. However the temporal association of Fas and FasL expression to the allergen-induced inflammatory changes is not well described. We hypothesize that the onset and resolution of the allergic airway response is associated with a time-dependent regulation of Fas-FasL expression. METHODS: Balb/c mice were sensitized to Af/alum on days 0 and 14, and challenged by Af on day 27. Lung function measurements (Penh), BAL inflammatory cell and cytokine profile, and soluble Fas and FasL levels were analyzed every 24h for up to day 4 and then at day 7 and 14 after intranasal provocation. Whole lung RNA was quantified by real-time PCR. RESULTS: Af challenge of sensitized mice induced acute increases in Penh, release of IL-4, IL-5 and neutrophil influx (22%) that peaked at 24h but resolved by 72h. Eosinophilia however persisted for a week (36%) before complete resolution by day 14. Fas was present at baseline in the BALF of naí¯ve mice (105 pg/ml) and rose slightly after allergen challenge (139 pg/ml). In contrast, BALF FasL was undetectable at baseline and showed a gradual increase over time (peak 190 pg/ml) with commensurate mRNA expression after Af challenge. CONCLUSIONS: Thus, a late onset of FasL expression preceded resolution of airway eosinophilia. Time-dependent regulation of FasL-mediated apoptosis may be responsible for prevention of prolonged presence of eosinophils in the airways after allergen exposure. Support: R01HL07664(JZ), R01AI055593(AH), ALA RG144N(AH)

abstract No: 


Full conference title: 

2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2006 (62nd)