Treatment with Flt3 ligand plasmid reverses allergic airway inflammation in ovalbumin-sensitized and -challenged mice Jehad H. Edwan a , James E. Talmadge b , Devendra K. Agrawal a,c,d, * a Department of Medical Microbiology and Immunology, Creighton University School of Medicine, CRISS I Room 131, 2500 California Plaza, Omaha, NE 68178, United States b Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States c Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, United States d Department of Medicine, Creighton University School of Medicine, Omaha, NE 68178, United States Received 13 October 2004; accepted 13 October 2004 Abstract We have previously reported that fms-like tyrosine kinase 3 ligand (Flt3-L) prevents and reverses established allergic airway inflammation in an ovalbumin (OVA) induced mouse model of asthma. In this study, we investigated the effect of pUMVC3- hFLex, a plasmid, mammalian expression vector for the secretion of Flt3-L on the same mouse model as well as the duration of the effect of the treatment. Allergic airway inflammation to OVA was established in BALB/c mice. OVA-sensitized mice received three intramuscular (i.m.) injections of 200 Ag pUMVC3-hFLex over 10 days. The response to pUMVC3-hFLex therapy was assessed based on airway hyperresponsiveness (AHR) to methacholine and inflammation, measured as serum cytokine and immunoglobulins (Ig) levels, and the total and differential cells in bronchoalveolar lavage fluid (BALF). pUMVC3-hFLex treatment completely reversed established AHR ( Pb0.01) and this effect lasted for at least 24 days after the last treatment injection ( Pb0.001). pUMVC3-hFLex treatment significantly increased BALF interferon-gamma (IFN-g) ( Pb0.01), serum interleukin (IL)-10 ( Pb0.01) and anti-OVA IgG2a levels ( Pb0.01). In contrast, serum IL-4 and IgE levels were significantly reduced ( Pb0.05). Total BALF cellularity, eosinophiles counts and BALF IL-5 levels were also reduced 1567-5769/$ - see front matter D 2004 Published by Elsevier B.V. doi:10.1016/j.intimp.2004.10.002 Abbreviations: Ab, antibody; Ag, antigen; AHR, airway hyperresponsiveness; ACT, ammonium chloride Tris; APCs, antigen presenting cells; DC, dendritic cells; BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; ELISA, enzyme-linked immunosorbent assay; Flt3-L, fms-like tyrosine kinase 3 ligand; IFN-g, interferon-gamma; Ig, immunoglobulin; IL, interleukin; i.m., intramuscular; i.p., intraperitoneal; OVA, ovalbumin; pDCs, plasmacytoid DCs; PBS, phosphate buffer saline; TGF-h, transforming growth factor-beta; TH, T helper. * Corresponding author. Department of Biomedical Sciences, Medicine, and Medical Microbiology and Immunology, Creighton University School of Medicine, CRISS I Room 131, 2500 California Plaza Omaha, NE 68178, United States. Tel.: +1 402 280 2938; fax: +1 402 280 1421. E-mail address: dkagr@creighton.edu (D.K. Agrawal). International Immunopharmacology 5 (2005) 345 – 357 www.elsevier.com/locate/intimp