Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin:cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide.
Normal rat bile contains secretory platelet-activating factor acetylhydrolase (PAF-AH), the enzyme capable of hydrolyzing the inflammatory mediator platelet-activating factor (PAF), and phospholipids containing oxidized truncated fatty acids. Because lecithin:cholesterol acyltransferase (LCAT) possesses intrinsic PAF-AH-like activity, it also may represent a potential anti-inflammatory enzyme. The behavior of PAF-AH and LCAT in hepatobiliary inflammatory responses in vivo has not been characterized. We therefore investigated the biliary and plasma secretion and pharmacological characteristics of these enzymes in rats subjected to intraportal bacterial endotoxin exposure (lipopolysaccharide [LPS], Escherichia coli, 055:B5). Portal vein LPS infusion (1 mg/kg, bolus) resulted in a maximal 4- to 5-fold increase in bile PAF-AH-specific activity with a gradual decline to baseline by 18 hours. Biliary PAF-AH hydrolyzed also the truncated sn-2-succinoyl and sn-2-glutaroyl analogs of PAF, indicating a broader activity of PAF-AH in bile toward byproducts of glycerophospholipid peroxidation. Plasma PAF-AH activity was not altered 5 hours after LPS injection compared with saline injection, but it was significantly elevated 18 hours after endotoxin exposure. The levels of LCAT in bile were low and declined to nearly undetectable values by 5 hours after cannulation in both control and LPS-exposed rats. Plasma LCAT activity was significantly increased after 5 hours and decreased 18 hours after LPS injection. In summary, hepatic exposure to endotoxin results in a rapid increase in biliary secretion of PAF-AH followed by elevation of LCAT and PAF-AH levels in plasma. We propose that biliary secretion of PAF-AH may be involved in the hepatic response to endotoxic insult by counteracting potential inflammatory damage in the biliary tree and gastrointestinal tract, whereas plasma increases in LCAT and PAF-AH may promote elimination of excess PAF and oxidized phospholipids in the circulation.
Svetlov
S I
SI
Program in Gastrointestinal Pathology, Yale Liver Center and Yale University Medical School, New Haven, CT, USA.
Sturm
E
E
Olson
M S
MS
Crawford
J M
JM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004926:Escherichia coli; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood / Q000378:metabolism*; D010741:Phospholipases A / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D008070:Lipopolysaccharides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase