Heterogeneity of human eosinophil glucocorticoid receptor expression in hypereosinophilic patients: absence of detectable receptor correlates with resistance to corticotherapy.
Abstract
Assessment of steroid receptor content in human neoplastic lymphoid cells or mammary tumour cells has been previously used to predict steroid sensitivity in various types of cancers. In the present study, we have evaluated the relationship between glucocorticoid receptor content and the glucocorticoid sensitivity of human eosinophils, since hypereosinophilic patients do not always respond favourably to glucocorticoid, particularly in the hypereosinophilic syndrome (HES). Blood or alveolar eosinophils obtained from seven patients (four with HES without leukaemic markers; two with parasitic diseases; and one with eosinophilic pneumonia) displayed the same specific glucocorticoid receptor content as normal eosinophils (7.58 +/- 1.31 x 10(3) versus 7.76 +/- 0.74 x 10(3) sites/cell). In contrast, glucocorticoid-binding sites were undetectable in purified eosinophils collected from seven HES patients with (n = 3) or without (n = 4) leukaemic markers, whilst their mononuclear cells and/or neutrophils bound glucocorticoid. In one HES patient, kinetic studies showed that blood eosinophils initially positive in glucocorticoid binding assays became negative with the subsequent appearance of leukaemic markers. The absence of specific glucocorticoid binding sites was correlated with the absence of glucocorticoid receptor proteins by the use of a specific anti-glucocorticoid receptor monoclonal antibody. Eosinophil sensitivity to glucocorticoid was investigated by the evaluation of glucocorticoid inhibition of eosinophil chemotaxis and by the clinical outcome of in vivo glucocorticoid therapy. Our data provide evidence of the heterogeneity of eosinophil glucocorticoid receptor expression. In addition, the presence of glucocorticoid receptors is a prerequisite for glucocorticoid activity, in vitro and in vivo, on cells of the eosinophil lineage.