Inducible expression and regulation of the alpha(1)-acid glycoprotein geneby alveolar macrophages: Prostaglandin E-2 and cyclic AMP act as new positive stimuli

We have reported that alpha(1)-acid glycoprotein (AGP) gene expression was induced in lung tissue and in alveolar type II cells during pulmonary infla mmatory processes, suggesting that local production of this immunomodulator y protein might contribute to the modulation of inflammation within the alv eolar space, Because AGP may also be secreted by other cell types in the al veolus, we have investigated the expression and the regulation of the AGP g ene in human and rat alveolar macrophages. Spontaneous AGP secretion by alv eolar macrophages was increased 4-fold in patients with interstitial lung i nvolvement compared with that in controls. In the rat, immunoprecipitation of [S-35]methionine-labeled cell lysates showed that alveolar macrophages s ynthesize and secrete AGP, IL-1 beta had no effect by itself, but potentiat ed the dexamethasone-induced increase in AGP production. RNase protection a ssay demonstrated that AGP mRNA, undetectable iin unstimulated cells, was i nduced by dexamethasone. Conditioned medium from LPS-stimulated macrophages as well as IL-1 beta had no effect by themselves, but potentiated the dexa methasone-induced increase in AGP mRNA levels. In addition to cytokines, PG E, as well as dibutyryl cAMP increased AGP mRNA levels in the presence of d examethasone. When AGP expression in other cells of the monocyte/macrophage lineage was examined, weak and no AGP production by human blood monocytes and by rat peritoneal macrophages, respectively, were observed. Our data sh owed that 1) AGP expression is inducible specifically in alveolar macrophag es in vivo and in vitro; and 2) PGE(2) and cAMP act as new positive stimuli for AGP gene expression.