Immune cell infiltration and broncovascular remodeling after nitric acid nasal instillation in a mouse bronchiolitis obliterans model.

Immune cell airway infiltration and the bronchovascular remodeling process have shown to be promising in the understanding of bronchiolitis obliterans (BO) pathogenesis. In this study we sought to validate the importance of immune cells, whether diffusely distributed or forming lymphoid follicles, collagen density, and vascular factors. Eight weeks after a single nitric acid (NA) nasal instillation, lung changes were characterized by lumen distortion, epithelial layer folding, reduction or total obliteration of terminal bronchiole (TB) lumen, and wall thickness increase. The morphologic changes in the TB and TA (terminal artery) lumen coincide with the measurement difference in the three groups. The TB diameter and lumen were significantly decreased in BO when compared with non-BO lungs (0.76 +/- 0.05 microm vs. 0.81 +/- 0.05 microm and 12,286.13 +/- 378.83 microm vs. 18,182.27 +/- 5,593.98 microm, p = 0.05 and p = 0.01, respectively). Equally significant was the increase in TB thickness in BO when compared with the non-BO group (201.72 +/- 35.75 microm vs. 149.75 +/- 40.61 microm, p = 0.007). The morphologic changes in immune cells seen in TB, TA, and bronchus-associated lymphoid tissue (BALT) also coincide with the quantification differences observed in the three groups. We concluded that immune cell infiltration and collagen/vascular remodeling are related to the spectrum of histologic changes in a BO nasal-induced model in mice and may be an appropriate target for prospective studies of human bronchiolitis.