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Influence of endogenous cortisol on eosinophil function in sensitized pigs: direct measurements of eosinophil peroxidase
Author(s) -
FORNHEM C.,
PETERSON C. G. B.,
SCHEYNIUS A.,
ALVING K.
Publication year - 1996
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.1996.tb00564.x
Subject(s) - eosinophil peroxidase , eosinophil , infiltration (hvac) , medicine , bronchoalveolar lavage , immunology , eosinophil cationic protein , lung , endocrinology , pathology , asthma , physics , thermodynamics
Summary Background and Objectives Eosinophils are associated with bronchial asthma, but the role of the eosinophil is not fully understood. This study was initiated in order to study the influence of endogenous cortisol on eosinophil recruitment and activation in allergic inflammation in the lower airways in the pig. Methods Polyclonal and monoclonal antibodies against porcine eosinophil peroxidase (EPO) were raised. Detection of eosinophils in blood smears and lung biopsy specimens was achieved using the polyclonal antibody. For determination of porcine EPO in bronchoalveoiar lavage (BAL) fluid, a sandwich enzyme‐linked immuno‐sorbent assay (ELISA) with a detection limit of 0.15μig/L was developed. No cross‐reactivity with porcine myeloperoxidase was found. Pigs that had been actively sensitized with repeated subcutaneous injections of Ascaris suum antigen were acutely challenged with antigen in the lower airways under pentobarbitone anaesthesia. Results Control animals with plasma cortisol levels of approximately 400 nM did not exhibit infiltration of eosinophils into lung parenchyma or EPO‐release in the bronchial lumen within 8 h after challenge. However, in pigs treated with a cortisol‐synthesis inhibitor (metyrapone), resulting in plasma cortisol levels of approximately 40 nM, there was a marked eosinophil infiltration into lung tissue at 8 h. Furthermore, EPO levels in BAL fluid were increased in some, although not all, low‐cortisol animals. There was no infiltration of eosinophils into skin tissue in these animals. Conclusions It is concluded that, after allergen challenge in the lower airways of metyrapone‐treated pigs, newly recruited eosinophils infiltrate lung tissue specifically. Furthermore, a cortisol‐sensitive release of the eosinophil‐derived cationic protein EPO, into the bronchial lumen was established. This is, to our knowledge, the first description of direct measurements of the release of an eosinophil granule protein in a large animal model of allergy.