Chelerythrine chloride induces rapid polymorphonuclear leukocyte apoptosisthrough activation of caspase-3

Polymorphonuclear leukocytes (PMN) play a primary role in the initiation an d propagation of inflammatory responses. PMN apoptosis is a major mechanism associated with the resolution of inflammatory reactions. Understanding me chanisms associated with PMN apoptosis will be of critical value in the dev elopment of novel pharmacological treatment strategies for local and/or sys temic inflammatory disorders. The present study demonstrates that cheleryth rine chloride induces human PMN to undergo rapid and synchronous progressio n into the apoptotic process via a PKC-independent mechanism. The appearanc e of the morphological features of apoptosis in chelerythrine-treated PMN i s preceded by a significant upregulation in caspase-3 activity. GM-CSF (a c ytokine that protects PMN in several models of PMN apoptosis) does not prot ect PMN from chelerythrine chloride-induced apoptosis.