Flt-3 ligand reverses late allergic response and airway hyper-responsiveness in a mouse model of allergic inflammation.
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 microg 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-alpha, 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.
Edwan
Jehad H
JH
Department of Medical Microbiology and Immunology, and Center for Allergy, Asthma, and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
Perry
Greg
G
Talmadge
James E
JE
Agrawal
Devendra K
DK
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D008024:Ligands; D008565:Membrane Proteins; C084881:flt3 ligand protein; D007073:Immunoglobulin E; D010047:Ovalbumin