Aspergillus fumigates-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice

The differential regulation of pulmonary surfactant proteins (SPs) is demon strated in a marine model of Aspergillus fumigatus (Af)-induced allergic ai rway inflammation and hyperresponsiveness. BALB/c mice were sensitized intr aperitoneally and challenged intranasally with Af extract. Enzyme-linked im munosorbent assay analysis of serum immunoglobulin (Ig) levels in these mic e showed markedly increased total IgE and Af-specific IgE and IgG1. This wa s associated with peribronchial/perivascular tissue inflammation, airway eo sinophilia, and secretion of interleukin (IL)-4 and IL-5 into the bronchoal veolar lavage fluid (BALF). Functional analysis revealed that in comparison with nonsensitized mice, allergic sensitization and challenge resulted in significant increases in acetylcholine responsiveness. To analyze levels of SPs, the cell-free supernate of the BALF was further fractionated by high- speed (20,000 x g) centrifugation. After sensitization and Challenges, the pellet (large-aggregate fraction) showed a selective downregulation of hydr ophobic SPs SP-B and SP-C by 50%. This reduction was reflected by commensur ate decreases in SP-B and SP-C messenger RNA (mRNA) expression of the lung tissue of these animals. In contrast, there was a 9-fold increase in SP-D p rotein levels in the 20,000 x g supernate without changes in SP-D mRNA. The increased levels of SP-D showed a significant positive correlation with se rum IgE (r = 0.85, P < 0.001). Tissue mRNA and protein levels of SP-A in ei ther the large- or the small-aggregate fractions were unaffected. Our data indicate that allergic airway inflammation induces selective inhibition of hydrophobic SP synthesis accompanied by marked increases in the lung collec tin SP-D protein content of BALF. These changes may contribute significantl y to the pathophysiology of Af-induced allergic airway hyperresponsiveness.