Effect of exogenous opioid peptides on TNF-alpha-induced human neutrophil apoptosis in vitro.
Polymorphonuclear leukocyte (neutrophil) apoptosis is an important mechanism regulating the life span and some functions of neutrophils at inflamed sites. Opioid peptides are present in the peripheral circulation and their concentrations rapidly increase as a result of stress and inflammation. The effect of opioid peptides such as met-enkephalin (M-ENK) and beta-endorphin (beta-END) on tumor necrosis factor (TNF)-alpha-induced apoptosis in human neutrophils in vitro was investigated. Neutrophils isolated from peripheral blood were cultured in the absence or presence of 10(-6)-10(-10) M of opioid peptides for 8, 12 and 18 h. Features of apoptotic neutrophils were measured by a flow cytometric method based on analysis of the apoptotic nuclei (DNA content). We found that M-ENK and beta-END enhanced both uninduced and TNF-alpha-induced neutrophil apoptosis in vitro in a dose-dependent manner. The effect of opioid peptides on the modulation of neutrophil apoptosis was not reversed by the opioid-receptor antagonist naloxone. The results suggest that M-ENK and beta-END can regulate neutrophil life span via apoptosis and in this way may participate in the resolution of inflammation.
Sułowska
Zofia
Z
Microbiology and Virology Center, Polish Academy of Sciences, Lódź, Poland. zsulowsk@cmiwpan.lodz.pl
Majewska
Ewa
E
Tchórzewski
Henryk
H
Klink
Magdalena
M
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006801:Humans; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D001615:beta-Endorphin / Q000494:pharmacology*
D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D004247:DNA