The absence of the VPAC(2) receptor does not protect mice from Aspergillus induced allergic asthma.
Allergic asthma is a T(H)2-mediated disease marked by airway inflammation, increased mucus production, and elevated serum IgE in response to allergen provocation. Among its ascribed functions, the neuropeptide vasoactive intestinal peptide (VIP) is believed to promote a T(H)2 phenotype when signaling through its VPAC(2) receptor. In this study, we assessed the requirement for the VIP/VPAC(2) axis in initiating the allergic pulmonary phenotype in a murine model of fungal allergic asthma. C57BL/6 wild-type (WT) and VPAC(2) knock-out (KO) mice were sensitized with Aspergillus fumigatus antigen and challenged with an aerosol of live conidia to induce allergic airways disease. WT and KO mice exhibited similar peribronchovascular inflammation, increased number of goblet cells, and elevated serum IgE. However, the absence of VPAC(2) receptor resulted in a marked enhancement of MUC5AC mRNA with an associated increase in goblet cells and a reduction in eosinophils in the airway lumen at day 3 when VIP mRNA was undetectable in the KO lung. Sustained elevation of serum IgE was noted in KO mice at day 14, while the level in WT mice declined at this time point. These data suggest that the absence of VPAC(2) does not protect mice from developing the signs and symptoms of allergic asthma.
Samarasinghe
A E
AE
Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108-6050, USA. a.samarasinghe@ndsu.edu
Hoselton
S A
SA
Schuh
J M
JM
D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001230:Aspergillus / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D020397:Goblet Cells / Q000473:pathology; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000096:biosynthesis; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000172:deficiency* / Q000502:physiology
D000946:Antigens, Fungal; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D051239:Receptors, Vasoactive Intestinal Peptide, Type II