Chelerythrine chloride induces rapid polymorphonuclear leukocyte apoptosis through activation of caspase-3.
Polymorphonuclear leukocytes (PMN) play a primary role in the initiation and propagation of inflammatory responses. PMN apoptosis is a major mechanism associated with the resolution of inflammatory reactions. Understanding mechanisms associated with PMN apoptosis will be of critical value in the development of novel pharmacological treatment strategies for local and/or systemic inflammatory disorders. The present study demonstrates that chelerythrine chloride induces human PMN to undergo rapid and synchronous progression into the apoptotic process via a PKC-independent mechanism. The appearance of the morphological features of apoptosis in chelerythrine-treated PMN is preceded by a significant upregulation in caspase-3 activity. GM-CSF (a cytokine that protects PMN in several models of PMN apoptosis) does not protect PMN from chelerythrine chloride-induced apoptosis.
Sweeney
J F
JF
Surgery Service, Ann Arbor Veterans Affairs Medical Center and Department of Surgery, University of Michigan, 48109, USA.
Nguyen
P K
PK
Atkins
K B
KB
Hinshaw
D B
DB
D000470:Alkaloids; D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C016299:chelerythrine; D011493:Protein Kinase C; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases