Segmental antigen challenge increases fibronectin in bronchoalveolar lavage fluid

Fibronectin may contribute to asthma pathogenesis by recruitment and activa tion of inflammatory cells, and by promotion of subepithelial fibrosis. Fib ronectin is produced by several types of airway cells, including epithelial cells, fibroblasts, and alveolar macrophages. To test the hypothesis that antigen-induced airway inflammation is associated with increased local gene ration of fibronectin, segmental bronchoprovocation (SBP) with antigen and saline was performed in 17 atopic patients. Bronchoalveolar lavage (BAL) wa s performed at 5 min and 48 h after segmental challenge with saline or anti gen. Fibronectin concentrations in BAL fluid, measured by enzyme-linked imm unosorbent assay (ELISA), increased more than 5-fold 48 h after antigen cha llenge (65 [47 to 110] versus 407 [240 to 697] ng/ml, median and 25 to 75% interquartiles, p < 0.05). Fibronectin concentrations 48 h after antigen ch allenge correlated with histamine concentrations 5 min after antigen challe nge and numbers of eosinophils, neutrophils, macrophages, and total cells i n BAL fluid 48 h after antigen challenge. BAL was more enriched in fibronec tin 48 h after challenge than would be predicted solely from increased perm eability of plasma proteins. Western blot analysis showed that fibronectin in BAL fluid was largely intact and contained the extra domain-A (ED-A) spl ice variant of cellular fibronectin, indicative of local production. We con clude that antigen challenge in atopic subjects causes increased production of fibronectin by airway cells and speculate that this response may contri bute to airway remodeling in allergic inflammation.