Local lung responses following local lung challenge with recombinant lungworm antigen in systemically sensitized sheep
| Autor: | D D, Collie, C N, MacAldowie, A D, Pemberton, C J, Woodall, N, McLean, C, Hodgson, M W, Kennedy, H R, Miller |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Sheep Neutrophils Serine Endopeptidases Cell Count Immunohistochemistry Bronchial Provocation Tests Recombinant Proteins Dictyocaulus Eosinophils Leukocyte Count Chymases Transforming Growth Factor beta Antigens Helminth Immunoglobulin G Models Animal Animals Female Immunization Mast Cells Bronchoalveolar Lavage Fluid Lung |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 31(10) |
| ISSN: | 0954-7894 |
| Popis: | 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.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.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 (BALF) (n = 16) and tissue (n = 3) were collected after the last challenge.Cellular changes 24 h after the fourth challenge were characterized by an increase in the absolute numbers of neutrophils and eosinophils in BALF 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-beta1 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.Mast cell phenotypic events occurring as a consequence of antigen challenge were limited to segments in which changes in BALF were characterized by neutrophil influx and increased local antibody production. |
| Databáze: | OpenAIRE |
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