Annexin 1 (ANXA1), a Ca2+ and phospholipid binding protein, is an important mediator of glucocorticoid (GC) action in the host defence and neuroendocrine systems (1). It is not however known whether the dysregulation of the inflammatory response sometimes observed in patients with disturbances in GC secretion is associated with alterations in PBL ANXA1 expression/activity. To address this question we have (a) examined ANXA1 expression (flow cytometry and western blot analysis) in PBLs from patients with endocrine diseases (primary or secondary adrenal disease, thyroid disease and diabetes) before and 30 and 60 min after administration of ACTH1-24 (250 microgram, i.v.) and (b) correlated the data with the serum cortisol concentration. The study was approved by Riverside Research Ethics Committee and patient consent was obtained. In comparison to patients with normal adrenal function, the expression of ANXA1 in PBLs (mainly neutrophils and monocytes) from patients with Cushing's was increased and correlated with the raised cortisol levels while PBLs from Addisonian patients showed reductions in ANXA1 expression which paralleled the low cortisol levels observed before and after injection of ACTH1-24. These finding support our hypothesis that changes in PBL ANXA1 expression may contribute to the altered susceptibility to autoimmune, inflammatory and infectious disease evident in states of GC dysbalance.
1. Buckingham JC & Flower RJ (1997) Mol Med Today 9, 296-302
We are grateful to the MRC and Wellcome Trust for financial support.
03 - 04 Dec 2001
Society for Endocrinology