In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response

• DOI: 10.1152/ajpregu.1999.277.1.r94
• Publication Date: 2017-12-25T07:36:51Z
• Authors: Riaz A. Memon; John Fuller; Arthur H. Moser; Kenneth R. Feingold; Carl Grunfeld
• Keywords: Lipopolysaccharides; Male; 0303 health sciences; Tumor Necrosis Factor-alpha; Turpentine; Zymosan; Phospholipases A; Rats; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cricetinae; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Splenectomy; Animals; RNA, Messenger; Acute-Phase Reaction; Interleukin-1

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.