-transparent.png){kind=logo}
BACKGROUND Activated neutrophils (PMNs) release cytotoxic agents that can damage surrounding tissue. These studies were performed to determine whether activated PMNs from rat could injure isolated, rat hepatic parenchymal cells (HCs) in vitro. METHODS HCs were cocultured with unstimulated rat PMNs or with PMNs activated with either f-met-leu-phe (FMLP) or phorbol myristate acetate (PMA), that stimulate predominantly degranulation or superoxide production, respectively. Toxicity to HCs was evaluated from release of alanine aminotransferase into the medium. RESULTS Alanine aminotransferase release was greater in HCs cocultured with FMLP- or PMA-stimulated PMNs compared with unstimulated PMNs. Toxicity was observed by 16 hours after stimulation of PMNs. To test the possible involvement of a soluble mediator released by activated PMNs, HCs were incubated with conditioned medium from PMNs. Compared with unstimulated PMNs, toxicity to HCs was greater in the presence of conditioned medium from FMLP-stimulated PMNs, but not conditioned medium from PMA-activated PMNs. Reactive oxygen species do not appear to be involved in the mechanism by which activated PMNs damage HCs since superoxide dismutase, catalase, superoxide dismutase+catalase, or desferrioxamine failed to prevent the injury. Furthermore, less superoxide anion was detected in PMA-stimulated PMNs when either HCs or HC-conditioned medium was present. Proteolytic enzymes released by stimulated PMNs may play a role in HC damage since an inhibitor of proteases diminished injury due to PMNs activated by either FMLP or PMA. CONCLUSIONS These results indicate that activated, rat PMNs damage HCs in culture. The data suggest that reactive oxygen species are not involved in the mechanism, but that release of proteolytic enzymes may play a role in the toxic response.
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
May 1996,
Journal of leukocyte biology,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
January 1978,
Josai Shika Daigaku kiyo. The Bulletin of the Josai Dental University,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
October 2011,
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
January 1996,
Drug metabolism and drug interactions,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
May 1994,
Toxicology and applied pharmacology,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
January 1982,
Josai Shika Daigaku kiyo. The Bulletin of the Josai Dental University,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
August 1996,
The Japanese journal of physiology,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
May 1984,
Biochemical and biophysical research communications,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
February 1986,
The American journal of physiology,
P E Ganey, and
M B Bailie, and
S VanCise, and
M E Colligan, and
B V Madhukar, and
J P Robinson, and
R A Roth
September 2008,
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis,
