[Morphological changes of non-apoptotic programmed cell death of polymorphonuclar neutrophils induced by ONO-AE-248].
OBJECTIVE
To investigate the morphological changes of polymorphonuclar neutrophils (PMNs) induced by ONO-AE-248, a selective agonist of EP3.


METHODS
The morphological changes of PMNs treated with or without ONO-AE-248 were observed by electron microscope, fluorescence microscope and confocal microscope.


RESULTS
A unique form of PMNs death was rapidly caused by ONO-AE-248. The agonist primarily induced morphological changes of PMN nucleus under electron microscope, including the fusion of the nuclear lobules same as a large round structure, decreasing of the compactness of chromatin, the blebbing and rupture of nuclear membrance. Observation of PMN nucleus under fluorescence microscope by DAPI staining gave the same conclusion. However, there were no apparent changes in other intracellular organelles. The structure and distribution of mitochondria of PMNs treated with ONO-AE-248 were different from the typical morphological changes of apoptotic PMNs. ONO-AE-248 exerted little effects on the exposure of cell membrane phosphatidylserine (PS).


CONCLUSIONS
ONO-AE-248 can promote the non-apoptotic programmed cell death of PMNs in vitro. The events occurring in nucleus and mitochondria might be the early features of the novel cell death, which suggests that nucleus and mitochondria may be the reaction center of PMNs induced by ONO-AE-248.
Zhang
Zi
Z
Laboratory of Molecular Biology, Luzhou Medical College, Luzhou 646000, China.
Liu
Jia-jia
JJ
Yao
Fu-li
FL
He
Hao
H
Yang
Jian
J
Xie
Hua-fu
HF
He
Tao
T
D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010120:Oxytocics / Q000494:pharmacology*
C121546:ONO AE 248; D010120:Oxytocics; D015232:Dinoprostone