Increased thromboxane A2 synthesis by rat lung neutrophils during selenium deficiency.
Modulation of cellular hydroperoxide levels is considered one of the important physiological mechanisms for regulating the synthesis of prostaglandins (PGs) and leukotrienes (LTs) in mammalian cells. Both vitamin E and selenium (Se) have the potential to affect the concentration of peroxides and, thus, the biosynthesis of eicosanoids. To gain insight into some of the molecular mechanisms underlying the regulation of the arachidonic acid cascade by vitamin E and Se, we have investigated the influence of altered vitamin E and Se nutrition on the ability of polymorphonuclear leukocytes (PMNs) derived from endotoxin-challenged lung to secrete arachidonic acid metabolites. Selenium deficiency had no significant effect (p > 0.05) on lavage fluid levels of thromboxane (TX) B2, LTB4 or LTC4. Vitamin E deficiency, however, led to a significant increase in LTB4 recovered from lavage fluid while having no effect on TXB2. In contrast, Se deficiency, although producing no discernible effects on the production of LTB4, resulted in a significant increase in the release of TXB2 by PMNs. An increase in TXB2 release was seen in both in vitro-stimulated and nonstimulated PMNs. Vitamin E deficiency appeared to induce an enhancement of LTB4 release by PMNs but the increase was not statistically significant. No detectable levels of LTC4 were found in PMN cultures stimulated with either zymosan or A23187. Thus, these studies indicate that deficiencies of either Se or vitamin E lead to alterations in the metabolism of arachidonic acid in the lung.
Eskew
M L
ML
Department of Veterinary Science, Pennsylvania State, University Park 16802.
Zarkower
A
A
Scheuchenzuber
W J
WJ
Hildenbrandt
G R
GR
Scholz
R W
RW
Reddy
C C
CC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D004032:Diet; D004926:Escherichia coli; D007975:Leukotriene B4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D051381:Rats; D012643:Selenium / Q000172:deficiency*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000378:metabolism
D008070:Lipopolysaccharides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D012643:Selenium