Effect of the MEK 1/2 inhibitor PD98059 on GM-CSF-induced neutrophil survival
| Time . | Control % apoptosis . | PD98059 % apoptosis . | GM-CSF % apoptosis . | GM-CSF/PD % apoptosis . | TNFα % apoptosis . | TNFα/PD % apoptosis . |
|---|---|---|---|---|---|---|
| 6 hrs | 12.6 ± 1.9 | 15.2 ± 2.0 | 3.7 ± 0.5* | 6.9 ± 2.6* | 40.8 ± 2.02-160 | 43.2 ± 4.12-160 |
| 20 hrs | 69.9 ± 4.8 | 77.2 ± 3.7 | 15.6 ± 5.0 | 37.2 ± 12.4 | 54.1 ± 4.3* | 60.6 ± 7.2 |
| Time . | Control % apoptosis . | PD98059 % apoptosis . | GM-CSF % apoptosis . | GM-CSF/PD % apoptosis . | TNFα % apoptosis . | TNFα/PD % apoptosis . |
|---|---|---|---|---|---|---|
| 6 hrs | 12.6 ± 1.9 | 15.2 ± 2.0 | 3.7 ± 0.5* | 6.9 ± 2.6* | 40.8 ± 2.02-160 | 43.2 ± 4.12-160 |
| 20 hrs | 69.9 ± 4.8 | 77.2 ± 3.7 | 15.6 ± 5.0 | 37.2 ± 12.4 | 54.1 ± 4.3* | 60.6 ± 7.2 |
Peripheral blood neutrophils were cultured in the presence or absence of GM-CSF (10 ng/mL) or TNFα (200 U/mL) with or without PD98059 (50 μM). Cells were harvested at 6 and 20 hours and cytospins fixed and stained as detailed in “Materials and methods.” Morphological assessment of neutrophil apoptosis demonstrated that inhibition of MEK1/2 by PD98059 had no effect on GM-CSF stimulated survival at 6 or 20 hours and had no effect on the early induction or late inhibition of apoptosis by TNFα. Data represent mean ± SEM of 6 independent experiments each performed in triplicate.
P < .05,
P < .005 compared to control values; P > .05 (NS) compared to corresponding values obtained in the absence of PD98059.