Local lung responses following local lung challenge with recombinant lungworm antigen in systemically sensitized sheep

Background Chronic mast cell-mediated inflammation may contribute significantly towards the extensive tissue remodelling that is a feature of lungworm infection in ruminants. Understanding the factors: that control tissue remodelling is a necessary step toward effective management and treatment of conditions that feature such pathology. Objective We sought to define in a novel ovine model system, the cellular, immune and mast cell phenotypic events that occur following local lung challenge with a recombinant protein antigen, DvA-1, derived from the ruminant lungworm nematode, Dictyocaulus viviparus. Methods Two spatially disparate lung segments in systemically sensitized sheep were challenged on three occasions with DvA-1(3xDVA and two further segments were challenged with saline (3xSAL). Two months after the third challenge, one of the two segments previously repeatedly challenged with DvA-1 was challenged again with DvA-1 (3xDVA:DVA) whilst the other was challenged with saline (3xDVA:SAL). A similar protocol was followed with the saline challenged segments. (3xSAL:SAL and 3xSAL:DVA. Bronchoalveolar lavage fluid (BALE): (n = 16) and tissue (n = 3) were collected after the last challenge. Results Cellular changes. 24 h after the fourth challenge were characterized by an increase in the absolute numbers of neutrophils and eosinophils in BALE from 3xDVA:DVA and 3xSAL:DVA segments. Local antibody production was implied through increased levels of antibody in both 3xDVA:DVA and 3xDVA:SAL segments, with the latter being unaffected by inflammation. Levels of active transforming growth factor beta-1 (TGF-beta (1)) were significantly increased in 3xDVA:SAL segments and a trend towards an increase was apparent in 3xDVA:DVA segments. Total TGF-beta (1) levels were significantly correlated with eosinophil counts in all except the 3xDVA:SAL segments. Such changes in the bronchoalveolar space were complemented by increased ratios of sheep mast cell proteinase-1 expressing cells and tryptase expressing cells, to toluidine blue positive cells in airways from 3xDVA:DVA segments. Conclusion Mast cell phenotypic events occurring as a consequence of antigen challenge were limited to segments in which changes in BALE were characterized by neutrophil influx and increased local antibody production.