Platelet-Activating Factor–Induced Ischemic Bowel Necrosis: The Effect of Platelet-Activating Factor Acetylhydrolase

Furukawa, Masayuki; Lee, Edward L.; Johnston, John M.

doi:10.1203/00006450-199308000-00027

Cited by 68 publications

(38 citation statements)

References 16 publications

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“…The level of plasma PAFacetylhydrolase activity also can be altered by acquired factors. Changes in the activity of plasma acetylhydrolase have been found in conjunction with asthma (38,45), systemic lupus erythematosus (46), hypertension (47,48), chronic cholestasis (49), and necrotizing entercolitis (50,51). In the case of clinical sepsis, two conflicting reports have been published.…”

Section: Discussionmentioning

confidence: 99%

Cell-specific Regulation of Expression of Plasma-type Platelet-activating Factor Acetylhydrolase in the Liver

Howard

Miller

Miwa

et al. 1997

Journal of Biological Chemistry

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Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that causes hypotension, increases vascular permeability, and has been implicated in anaphylaxis, septic shock and several other inflammatory responses. PAF is hydrolyzed and inactivated by the enzyme PAF-acetylhydrolase. In the intact rat, a mesenteric vein infusion of lipopolysaccharide (LPS) served as an acute, liver-focused model of endotoxemia. Plasma PAF-acetylhydrolase activity increased 2-fold by 24 h following LPS administration. Ribonuclease protection experiments demonstrated very low levels of plasma-type PAF-acetylhydrolase mRNA transcripts in the livers of saline-infused rats; however, 24 h following LPS exposure, a 20-fold induction of PAF-acetylhydrolase mRNA was detected. In cells isolated from endotoxin-exposed rat livers, Northern blot analyses demonstrated that Kupffer cells but not hepatocytes or endothelial cells were responsible for the increased PAF-acetylhydrolase mRNA levels. In Kupffer cells, plasma-type PAF-acetylhydrolase mRNA was induced by 12 h, peaked at 24 h, and remained substantially elevated at 48 h. Induction of neutropenia prior to LPS administration had no effect on the increase in PAF-acetylhydrolase mRNA seen at 24 h. Although freshly isolated Kupffer cells contain barely detectable levels of plasma-type PAF-acetylhydrolase mRNA, when Kupffer cells were established in culture, PAF-acetylhydrolase expression became constitutively activated concomitant with cell adherence to the culture plates. Alterations in plasma-type PAF-acetylhydrolase expression may constitute an important mechanism for elevating plasma PAF-acetylhydrolase levels and an important component in minimizing PAF-mediated pathophysiology in livers exposed to endotoxemia.

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Section: Discussionmentioning

confidence: 99%

Cell-specific Regulation of Expression of Plasma-type Platelet-activating Factor Acetylhydrolase in the Liver

Howard

Miller

Miwa

et al. 1997

Journal of Biological Chemistry

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“…Additionally, IFN-␥ and LPS decreased the human PAF acetylhydrolase promoter activity by 35% and 50% respectively in monocyte-derived macrophages and various established macrophage cell lines (11). However, changes in the in vivo activity of plasma PAF acetylhydrolase have been documented in conjunction with asthma (12), systemic lupus erythematosus (13), hypertension (14,15), chronic cholestasis (9), and necrotizing enterocolitis (16,17). In most cases, the levels of circulating PAF acetylhydrolase activity are increased as a physiological response to inflammatory stimuli.…”

mentioning

confidence: 99%

The Expression and Localization of Plasma Platelet-activating Factor Acetylhydrolase in Endotoxemic Rats

Howard

Olson

2000

Journal of Biological Chemistry

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The production of platelet-activating factor (PAF) and PAF-like phospholipids that also bind the PAF receptor are implicated in numerous pathological situations including bacterial endotoxemia and injury-induced oxidative damage. PAF and PAF-like phospholipids are hydrolyzed and inactivated by the enzyme PAF acetylhydrolase. In the intact rat, infusion of lipopolysaccharide (LPS) into a mesenteric vein served as an acute, liver-focused model of endotoxemia. We determined that the liver responds to LPS exposure with the production of plasma-type PAF acetylhydrolase mRNA and protein expression specifically in the resident macrophages of the liver. Liver macrophages, defined immunohistochemically using antibodies against ED1, present in livers from saline-treated animals contained no detectable PAF acetylhydrolase. Twenty-four hours following in vivo LPS administration, immunohistochemistry detected a slight increase in the number of ED1 staining cells and the ED1-positive cells now contained an abundance of PAF acetylhydrolase. The systemic administration of LPS resulted in increased expression of PAF acetylhydrolase in several tissues. Of the tissues examined, the greatest increase in PAF acetylhydrolase expression was observed in lung followed by increases in spleen, liver, kidney, and thymus. Additionally, the expression of PAF acetylhydrolase mRNA increased in circulating leukocytes and in peritoneal macrophages in response to systemic exposure to LPS. We examined the regulation of PAF acetylhydrolase expression and demonstrated the administration of the PAF receptor antagonists, BN 50739 and WEB 2170, inhibited by 50% the increase in PAF acetylhydrolase expression in response to LPS. The up-regulation of the plasma-type PAF acetylhydrolase expression constitutes an important mechanism for elevating the local and systemic ability to inactivate PAF and oxidized phospholipids in order to minimize PAF-mediated pathophysiology consequent from exposure to endotoxin. The abundance of PAF acetylhydrolase production in the liver lobule likely limits endotoxin-mediated tissue damage due to PAF synthesis.

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“…[13][14][15] In contrast, recombinant PAF-AH prevented the development of ischemia-elicited necrosis of the duodenum, jejunum, and ileum after injection of PAF into rat descending aorta. 16,17 PAF and PAF-AH are implicated in the pathogenesis of liver and inflammatory bowel diseases in humans including patients with cirrhosis of the liver and Crohn' s disease. [18][19][20] Thus, there is a compelling need to further characterize the hepatic biology of both PAF and PAF-AH.…”

mentioning

confidence: 99%

Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin: Cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide

et al. 1999

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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. (HEPATOLOGY 1999;30:128-136.)

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Platelet-Activating Factor–Induced Ischemic Bowel Necrosis: The Effect of Platelet-Activating Factor Acetylhydrolase

Cited by 68 publications

References 16 publications

Cell-specific Regulation of Expression of Plasma-type Platelet-activating Factor Acetylhydrolase in the Liver

Cell-specific Regulation of Expression of Plasma-type Platelet-activating Factor Acetylhydrolase in the Liver

The Expression and Localization of Plasma Platelet-activating Factor Acetylhydrolase in Endotoxemic Rats

Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin: Cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide

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