Treatment with Flt3 ligand plasmid reverses allergic airway inflammation in ovalbumin-sensitized and -challenged mice.
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 mug 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 (P<0.01) and this effect lasted for at least 24 days after the last treatment injection (P<0.001). pUMVC3-hFLex treatment significantly increased BALF interferon-gamma (IFN-gamma) (P<0.01), serum interleukin (IL)-10 (P<0.01) and anti-OVA IgG2a levels (P<0.01). In contrast, serum IL-4 and IgE levels were significantly reduced (P<0.05). Total BALF cellularity, eosinophiles counts and BALF IL-5 levels were also reduced (P<0.01). pUMVC3-hFLex treatment can reverse established experimental asthma and might provide a novel approach for treating asthma.
Edwan
Jehad H
JH
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, CRISS I Room 131, 2500 California Plaza, Omaha, NE 68178, USA.
Talmadge
James E
JE
Agrawal
Devendra K
DK
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000628:therapy*
D007136:Immunoglobulins; D015848:Interleukin-5; D008565:Membrane Proteins; C084881:flt3 ligand protein; D015847:Interleukin-4; D010047:Ovalbumin