REGULATION OF IGE-MEDIATED AIRWAY INFLAMMATION IN A MURINE CHALLENGE MODEL BY FAS LIGAND NEUTRALIZATION. FA Almeida, MD (3), S Sharma, PhD (1),
S Kierstein, PhD (3), L Hortobagyi, MSc (3), J Peterson, BS (1), H Yagita, PhD (4),
A Haczku, MD, PhD (3), and J Zangrilli*, MD (1,2). (1) Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA; (2) Division of Pulmonary and Critical Care, Thomas Jefferson University, Philadelphia, PA; (3) Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA, and (4) Juntendo University School of Medicine, Tokyo, Japan.
Pathogenically important cell-types in asthma/rhinitis (e.g. eosinophils, lymphocytes) are sensitive to Fas-mediated apoptosis, so Fas Ligand (FasL) activity should play a role in regulating the IgE-mediated response. To test this, we examined the inflammatory response under FasL neutralizing conditions in a murine challenge model. Aspergillus sensitized Balb/c mice were sacrificed 1, 7 and 10 days after intranasal challenge with the same (day 0). The study and control groups received neutralizing antibody to FasL (clone MFL4) or irrelevant antibody, respectively, via intraperitoneal injection on day 0 and day 5. BAL inflammatory cell profile and soluble FasL levels were analyzed. BAL eosinophil percent was similar in both groups on day 1 (47% and 57.4%, MFL4 and control, respectively), but diverged thereafter (day 7: 44% and 19%, day 10: 29% and 16%). Post-challenge BAL FasL levels were flat in the MFL4 group, but increased at day 7 in controls. FasL neutralization in a murine asthma model enhanced the allergic inflammatory response. These results are consistent with the hypothesis that endogenous FasL activity is important in down regulating allergic airway inflammation.
Funded By: RO1 HL076646-01A1, ALA RG-144-N, R01 AI055593-01A1
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