Cellular composition of Alternaria-induced airway inflammation
A. alternata increased the total number of cells in BALF in both C57Bl/6 mice (Figure 6A , B ; n = 3 mice per group) and BALB/c mice (Figure 6C, D; n = 4 mice per group). Differential cell counts demonstrated that the primary inflammation was due to increased eosinophils (increasing from 1,150 ± 450 cells to 18,000 ± 4,700 cells in C57/Bl-6 and from 240 ± 140 cells to 49,000 ± 15,000 cells in BALB/c), and lymphocytes (increasing from 2400 ± 821 to 16,000 ± 2656 cells in C57Bl/6 and 650 ± 550 to 12,000 ± 3,000 cells in BALB/c). In C57Bl/6 mice, 2.5 nM C391 reduced eosinophils and lymphocytes in the BALF by 90% (2100±750, 1700±500). Treatment with a lower concentration of C391 (0.25 nmoles) reduced eosinophils by 75% (4300±1900) and lymphocytes by 80% (3300±550). In BALB/c mice, treatment with 5 nM C391 reduced eosinophils in the BALF 50% (23,000 ± 756 cells) and lymphocytes by 80% (2,700 ± 476 cells), but only the reduction in lymphocytes was statistically significant (p < 0.05) compared to the A. alternata treatment. In BALB/c but not C57Bl/6 mice, A. alternata significantly increased the number of macrophages in the BALF (38,000 ± 610 cells to 95,000 ± 1,400 cells, respectively) and this was significantly reduced by C391 (48,000 ± 6,200 cells, p < 0.05). A minimal neutrophilic response was observed in both mouse strains and this was not reduced by C391. Taken together, these data support that A. alternata -mediated airway inflammation (infiltration of eosinophils and lymphocytes, epithelial thickening, and mucus overproduction) in C57Bl/6 and BALB/c mice, can be inhibited by the PAR2 antagonist, C391.