Surfactant Protein A Function in Asthma Is Defective as a Modulator of Inflammation during Infection

摘要

The exaggerated inflammatory response of asthmatic epithelial cells to in-vitro challenge with Mycoplasma pneumoniae (MP) has been previously described. Surfactant protein A (SP-A) attenuates this inflammatory response in nonasthmatic epithelial cells. Hypothesis: SP-A derived from patients with asthma is less effective in modulating inflammation than SP-A from normal subjects. Methods: Airway epithelial cells from 10 subjects with asthma (FEV_1: 81 ± 5% predicted) and 5 normal subjects (FEV_1: 95 ± 4% predicted) were cultured. SP-A was isolated from bronchoalveolar lavage by ultracentrifugation. After 14 days at an air-liquid interface, cells were exposed to normal (NSP-A) and asthmatic SP-A (A-SPA) separately or both combined 30 minutes before exposure to MP and incubated for 48 hours. IL-8 was determined by ELISA and MUC5AC mRNA by RT-PCR. Results: MP alone significantly increased MUC5AC and IL-8 expression above negative control only in asthmatic cells (P < 0.05). NSP-A significantly decreased IL-8 and MUC5AC from both groups (P < 0.05), but ASP-A did not attenuate MUC5AC and IL-8 expression significantly in either group compared with MP alone. The combination of NSP-A and ASP-A decreased expression of both mediators to the level of uninfected control, ruling out the presence of an inhibitor (Figure). Conclusions: A-SPA failed to abrogate inflammation associated with infection, suggesting one aspect of impaired innate immunity in asthma.