In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response.
Plasma platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes PAF and oxidized phospholipids and is associated with lipoproteins in the circulation. Endotoxin [lipopolysaccharide (LPS)], a potent inducer of the acute phase response (APR), produces marked changes in several proteins that play important roles in lipoprotein metabolism. We now demonstrate that LPS produces a 2.5- to 3-fold increase in plasma PAF-AH activity in Syrian hamsters. The plasma PAF-AH activity is found in the high-density lipoprotein (HDL) fraction and is increased threefold with LPS treatment despite a decrease in plasma HDL levels, indicating that plasma PAF-AH activity is increased per HDL particle. LPS markedly increased PAF-AH mRNA levels in liver, spleen, lung, and small intestine. The maximal increase in plasma PAF-AH activity and mRNA expression in liver and spleen is seen 24 h after LPS treatment. Both tumor necrosis factor and interleukin-1 modestly increased plasma PAF-AH activity and mRNA levels in liver and spleen, suggesting that they may partly mediate the effect of LPS on PAF-AH. Surgical removal of spleen had no effect on basal or LPS-induced plasma PAF-AH activity, suggesting that spleen per se may not contribute to plasma PAF-AH activity. Finally, LPS, turpentine and zymosan increased plasma PAF-AH activity in mice and/or rats, indicating that multiple APR inducers upregulate plasma PAF-AH and this effect is consistent across different rodent species. Taken together, our results indicate that plasma PAF-AH activity and mRNA expression is markedly upregulated during the host response to infection and inflammation. An increase in plasma PAF-AH may enhance the degradation of PAF as well as alter the structure and function of HDL during infection and inflammation.
Department of Medicine, University of California San Francisco CA 94143, USA. rmemon@itsa.ucsf.edu
R A
RA
Memon
J
J
Fuller
A H
AH
Moser
K R
KR
Feingold
C
C
Grunfeld
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000210:Acute-Phase Reaction / Q000201:enzymology*; D000818:Animals; D006224:Cricetinae; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014425:Turpentine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D014425:Turpentine