Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation

Jehad H. Edwan, Greg Perry, James E. Talmadge, Devendra K. Agrawal

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Abstract

Flt3 ligand (Flt3-L) is a growth factor for dendritic cells and induces type 1 T cell responses. We recently reported that Flt3-L prevented OVA-induced allergic airway inflammation and suppressed late allergic response and airway hyper-responsiveness (AHR). In the present study we examined whether Flt3-L reversed allergic airway inflammation in an established model of asthma. BALB/c mice were sensitized and challenged with OVA, and AHR to methacholine was established. Then mice with AHR were randomized and treated with PBS or 6 μg of Flt3-L i.p. for 10 days. Pulmonary functions and AHR to methacholine were examined after rechallenge with OVA. Treatment with Flt3-L of presensitized mice significantly suppressed (p <0.001) the late allergic response, AHR, bronchoalveolar lavage fluid total cellularity, absolute eosinophil counts, and inflammation in the lung tissue. There was a significant decrease in proinflammatory cytokines (TNF-α, IL-4, and IL-5) in bronchoalveolar lavage fluid, with a significant increase in serum IL-12 and a decrease in serum IL-5 levels. There was no significant effect of Flt3-L treatment on serum IL-4 and serum total IgE levels. Sensitization with OVA significantly increased CD11b+CD11c+ cells in the lung, and this phenomenon was not significantly affected by Flt3-L treatment. These data suggest that Flt3-L can reverse allergic airway inflammation and associated changes in pulmonary functions in murine asthma model.

Original languageEnglish
Pages (from-to)5016-5023
Number of pages8
JournalJournal of Immunology
Volume172
Issue number8
StatePublished - Apr 15 2004

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Respiratory Hypersensitivity
Inflammation
Methacholine Chloride
Interleukin-5
Bronchoalveolar Lavage Fluid
Serum
Interleukin-4
Lung
Asthma
flt3 ligand protein
Interleukin-12
Eosinophils
Dendritic Cells
Immunoglobulin E
Intercellular Signaling Peptides and Proteins
Pneumonia
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology

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Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation. / Edwan, Jehad H.; Perry, Greg; Talmadge, James E.; Agrawal, Devendra K.

In: Journal of Immunology, Vol. 172, No. 8, 15.04.2004, p. 5016-5023.

Research output: Contribution to journalArticle

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