Figure 6.
Treatment with BCL-XL inhibitor A-1331852 preferentially depletes lung-infiltrating neutrophils during airway inflammation in mice. B6 mice were sensitized to OVA protein by IP injection of alum/OVA or alum alone control on d0 and d7. After 3 weeks, mice were challenged daily for 4 consecutive days with aerosolized OVA. Mice were gavaged orally with either the BCL-XL inhibitor or vehicle on d4 after OVA challenge, and again the following morning 2 hours before organ harvest. (A) Schematic of the OVA model of airway inflammation. Upon end point, (B) BAL and (C) blood were collected and the number of viable neutrophils (PMN), eosinophils (Eos), and T cells were determined by PI staining and flow cytometry. Data shown is pooled from 2 experiments (n = 4-6 mice/group; mean ± SEM). All data were analyzed using a 2-tailed Student t test. *P < .05, **P < .01, ***P < .001. (D) PMN were cultured with various combinations of 1 µM BCL-XL inhibitor A-1331852, 2.5 µM DEX, and 0.1 ng/mL GM-CSF. After 16 hours, viable PMN were enumerated by flow cytometry. Data shown as mean ± SD of viable PMN per well. Data show a single representative experiment of n = 3 experiments. All data were analyzed using a 2-tailed Student t test. ***P < .001.