The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane.
Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.
Navarro
S
S
Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
Aleu
J
J
Jiménez
M
M
Boix
E
E
Cuchillo
C M
CM
Nogués
M V
MV
D002118:Calcium / Q000378:metabolism; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D047150:Eosinophil Cationic Protein / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D018613:Microscopy, Confocal; D010718:Phosphatidylserines / Q000378:metabolism; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D061945:Caspase Inhibitors; D008051:Lipid Bilayers; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D012313:RNA; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D002118:Calcium