Role of Ca2+ in activation of reactive oxygen species production in polymorphonuclear leukocytes during tumour growth in rats.
The role of Ca(2+) ions in PMA-induced generation of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNL) was studied during Zajdela hepatoma growth in the peritoneal cavity of rats. In PMNL from control healthy animals, a manifold Ca(2+)-induced enhancement of ROS generation and its significant reduction in the presence of Ca(2+) binding agent (BAPTA-AM) were observed. In contrast, ROS generation by PMNL from tumour-carrying animals dramatically increased in Ca(2+)-free medium, being practically insensitive to the agents, which can increase or decrease intracellular Ca(2+) levels. Free cytosolic Ca(2+) ([Ca(2+)](i)) in control PMNL was found to be relatively low ( approximately 250 nmol/L), rising slowly after Ca(2+) addition and further to two-fold in the presence of Ca(2+) and ionomycin in the incubating medium. Tumour growth in animals was accompanied with a significant [Ca(2+)](i) elevation. In Ca(2+)-free medium, [Ca(2+)](i) elevation was up to 480 nmol/L in tPMNL with the additions of Ca(+) and ionomycin as well as EGTA and ionomycin being able to increase [Ca(2+)](i) to 700-900 nmol/L onward. It was concluded that a higher Ca(2+) permeability of the plasma membrane and higher Ca(2+) accumulation in intracellular pools of PMNL was developed at the advanced stages of malignant disease. These results indicate the primed state of circulating PMNL and the independence of PMA-induced ROS generation at intra- and extracellular Ca(2+) levels at the advanced stages of tumour growth in animals.
Pustovidko
A
A
A. N. Belozersky Institute of Physicochemical Biology, Moscow State University, Moscow 119899, Russia. antonina.pustovidko@gmail.com
Potselueva
M
M
Kochegarov
A
A
Evtodienko
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D007700:Kinetics; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D002118:Calcium