PHENOTYPIC AND FUNCTIONAL MODULATION OF NORMAL HUMAN ALVEOLAR MACROPHAGES BY HISTAMINE

Alveolar macrophages (AM) play a regulatory role in asthma. AM from as thmatics are activated, release increased amounts of cytokines, and ex press higher levels of the low affinity receptor for IgE (Fc epsilon R IIb/CD23b) and receptors for adhesion molecules. The bronchial microen vironment may modulate the phenotypic and functional characteristics o f AM. On AM from normal subjects, the effects of histamine were studie d on the expression of adhesion molecules (LFA-1, ICAM-1) and CD23b as well as on the release of fibronectin. The expression of LFA-1, ICAM- 1, and CD23b was examined by immunocytochemistry using the alkaline ph osphatase-anti-alkaline phosphatase technique. The expression of CD23b mRNA was studied by in situ hybridization. The release of fibronectin was measured by enzyme immunoassay. We found that histamine induced i n a dose- and time-dependent fashion a significant increase of AM expr essing the three membrane markers and a significant increase in the re lease of fibronectin. The maximum effect of histamine was observed aft er an incubation of 12 to 24 h and a dose of 1 mu M. The histamine eff ects were specific, since they were significantly inhibited by an Hi-b locker pyrilamine, used at a concentration of 10 mu M. The effect of a n H-2-blocker (ranitidine, concentration of 10 mu M) was inconstant. C ycloheximide blocked the histamine effects, suggesting that it require s protein synthesis for its action. This study provides an in vitro mo del of cellular interaction between mast cells and AM, which might be relevant in the airway inflammation in asthma.