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 acetylhydrola se (PAF-AH), the enzyme capable of hydrolyzing the inflammatory mediator pl atelet-activating factor (PAF), and phospholipids containing oxidized trunc ated fatty acids. Because lecithin:cholesterol acyltransferase (LCAT) posse sses intrinsic PAF-AH-like activity, it also may represent a potential anti -inflammatory enzyme. The behavior of PAF-AH and LCAT in hepatobiliary infl ammatory responses in vivo has not been characterized. We therefore investi gated the biliary and plasma secretion and pharmacological characteristics of these enzymes in rats subjected to intraportal bacterial endotoxin expos ure (lipopolysaccharide [LPS], Escherichia coli, 055:B5). Portal vein LPS i nfusion (1 mg/kg, bolus) resulted in a maximal 4- to 5-fold increase in bil e 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-glutar oyl 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 level s 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 a ctivity was significantly increased after 5 hours and decreased 18 hours af ter LPS injection. In summary, hepatic exposure to endotoxin results in a r apid 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 ma y be involved in the hepatic response to endotoxic insult by counteracting potential inflammatory damage in the biliary tree and gastrointestinal trac t, whereas plasma increases in LCAT and PAF-AH may promote elimination of e xcess PAF and oxidized phospholipids in the circulation.