cyclin-dependent kinase 9 activity regulates neutrophil spontaneous apoptosis细胞周期蛋白依赖性激酶9活动自发调节中性粒细胞凋亡.pdfVIP

Cyclin-Dependent Kinase 9 Activity Regulates Neutrophil Spontaneous Apoptosis 1. 1. 1 2 2 3 Keqing Wang , Peter Hampson , Jon Hazeldine , Vladimir Krystof , Miroslav Strnad , Paul Pechan , Janet M. Lord1* 1 MRC Centre for Immune Regulation, Institute of Biomedical Research, Birmingham University Medical School, Birmingham, United Kingdom, 2 Laboratory of Growth ´ Regulators, Institute of Experimental Botany ASCR and Palacky University, Olomouc, Czech Republic, 3 C3Bio Ltd, Munich, Germany Abstract Neutrophils are the most abundant leukocyte and play a central role in the immune defense against rapidly dividing bacteria. However, they are also the shortest lived cell in the blood with a lifespan in the circulation of 5.4 days. The mechanisms underlying their short lifespan and spontaneous entry into apoptosis are poorly understood. Recently, the broad range cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to increase neutrophil apoptosis, implicating CDKs in the regulation of neutrophil lifespan. To determine which CDKs were involved in regulating neutrophil lifespan we first examined CDK expression in human neutrophils and found that only three CDKs: CDK5, CDK7 and CDK9 were expressed in these cells. The use of CDK inhibitors with differing selectivity towards the various CDKs suggested that CDK9 activity regulates neutrophil lifespan. Furthermore CDK9 activity and the expression of its activating partner cyclin T1 both declined as neutrophils aged and entered apoptosis spontaneously. CDK9 is a component of the P-TEFb complex involved in transcriptional