Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids.
Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 microgramgs twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 ng/10(6) AMs; 4.4 ng/10(6) ATII cells) and secreted (1. 4 ng/10(6) AMs; 1.8 ng/10(6) ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10(-7) M dexamethasone but at 10(-3) M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.
Hall
S E
SE
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London W6 8RF, United Kingdom.
Lim
S
S
Witherden
I R
IR
Tetley
T D
TD
Barnes
P J
PJ
Kamal
A M
AM
Smith
S F
SF
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019819:Budesonide / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology*; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide; D003907:Dexamethasone