Generation of reactive oxygen species and activity of platelet-activating factor acetylhydrolase in human monocyte-derived macrophages.
Monocytes were prepared from healthy human volunteers and were allowed to differentiate into macrophages by adhesion to plastic surface and cultured over 7 days in presence of either 10% fetal calf serum (FCS), human control serum or serum from hyperlipaemic patients. Hyperlipaemic serum stimulated the differentiation (measured as an increase in cellular protein and DNA content) to a higher extent when compared to control serum and FCS. With all sera a marked increase of the cellular activity of the enzyme platelet-activating factor acetylhydrolase (PAF-AH) and a tremendous decrease in the capacity of cells to generate reactive oxygen species (ROS) was observed. After seven days of culture the increase in PAH-AH activity was about 19-fold with hyperlipaemic serum, 11-fold with control serum and 6-fold with FCS. During the same period of time ROS generation measured as zymosan-induced chemiluminescence decreased by about 98% and no significant differences between the three types of serum were found. The results indicate that the activity of PAF-AH and the capacity of ROS generation which are both assumed to play an important role in the oxidation of low-density lipoproteins (LDL) and thus in the development of atherosclerosis, change in opposite direction during the differentiation of blood monocytes into macrophages, and that hyperlipaemic serum stimulates PAF-AH activity but not ROS generation.
Russwurm
S
S
Research Centre for Vascular Biology and Medicine Erfurt, University of Jena, Germany.
Krause
S
S
Finkelberg
L
L
Rühling
K
K
Schauer
U
U
Lösche
W
W
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D010741:Phospholipases A / Q000097:blood*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values
D017382:Reactive Oxygen Species; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase