Anti-inflammatory properties of a platelet-activating factor acetylhydrolase

  title={Anti-inflammatory properties of a platelet-activating factor acetylhydrolase},
  author={Larry W. Tjoelker and Cheryl L. Wilder and Christine Eberhardt and Diana M. Stafforinit and Gregory N. Dietsch and Brian A. Schimpf and Shawnee Hooper and Hai Le Trong and Lawrence S. Cousens and Guy A Zimmerman and Yoshiji Yamadat and Thomas M. Mclntyre and Stephen M. Prescott and Patrick W. Gray},
PLATELET-ACTIVATING factor (PAF) is a potent pro-inflammatory phospholipid that activates cells involved in inflammation1,2. The biological activity of PAF depends on its structural features, namely an ether linkage at the sn-1 position and an acetate group at the sn-2 position. The actions of PAF are abolished by hydrolysis of the acetyl residue, a reaction catalysed by PAF acetylhydrolase. There are at least two forms of this enzyme-one intracellular and another that circulates in plasma and… 

Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase.

This review will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation, namely the intracellular types I and II and a plasma type.

The structure and function of platelet-activating factor acetylhydrolases

Abstract. Platelet-activating factor acetylhydrolases (PAF-AHs, EC constitute a unique and biologically important family of phospholipase A2s. They are related to neither the

Platelet-activating Factor Acetylhydrolases*

The nature of the substrates hydrolyzed by PAF acetylhydrolases points at key roles for these activities in physiology and pathology, and it has provided important clues into what is currently thought to be the main function of these enzymes, which is to act as scavengers of bioactive phospholipids.

Roles of plasma platelet-activating factor acetylhydrolase in allergic, inflammatory, and atherosclerotic diseases.

Insight is provided into the functions of PAF and oxidized phospholipids as well as into the etiology of allergic, inflammatory, and atherosclerotic diseases.

To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

This review seeks to address concerns around the functional role of the plasma form of platelet-activating factor acetylhydrolase, and addresses concerns of structurally related multiple ligands for PAF-R with varied potency and continuous PAF production by the so called bi-cycle of PAF makes PAF more enigmatic.

Crystal Structure of Human Plasma Platelet-activating Factor Acetylhydrolase

The model of interface binding begins to explain the known specificity of lipoprotein-bound substrates and how the active site can be both close to the hydrophobic-hydrophilic interface and at the same time be accessible to the aqueous phase.

Identification of platelet-activating factor acetylhydrolase II in human skin.

Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apop tosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation, and evidence that this specialized phospholipase is involved in protecting this organ against oxidative stress through the degradation of oxidatively modified bioactive phospholIPids is provided.

Biology of Platelet-activating Factor Acetylhydrolase (PAF-AH, Lipoprotein Associated Phospholipase A2)

Current knowledge related to the structural features of PAF-AH are discussed, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation, which suggests that increased expression of this enzyme is a physiological response to inflammatory stimuli.



Secretion of platelet-activating factor acetylhydrolase following phorbol ester-stimulated differentiation of HL-60 cells.

The stimulation of PAF-AH secretion during differentiation of HL-60 cells and its modulation by LPS and steroid hormones may provide a useful model system for studying PAF metabolism during the inflammatory response and pregnancy.

Platelet-activating factor: a phospholipid autacoid with diverse actions.

PAF is unique in its role as a phospholipid that functions as an intercellular mediator, and it may also function as an intracellular messenger.

Human macrophages secret platelet-activating factor acetylhydrolase.

Macrophages secrete an enzyme that inactivates lipid mediators at sites of inflammation and in plasma, and these changes during the maturation of monocytes to macrophages may serve to limit the acute inflammatory response.

Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.

Results suggest that deficiency of serum PAF acetylhydrolase might be one of the factors leading to severe respiratory symptoms in asthmatic children.

The catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase.

Cloned the cDNA for the 29-kDa catalytic subunit of brain PAF acetylhydrolase and isolated and sequenced the [3H]DFP-labeled peptide fragment, revealing that Ser47 is the active serine residue.

Platelet-activating factor (PAF) stimulates the production of PAF acetylhydrolase by the human hepatoma cell line, HepG2.

The liver may be a major source of plasma PAF acetylhydrolase, and PAF may induce the production of its inactivating enzyme by the liver.

Release of platelet-activating factor in systemic lupus erythematosus.

The protein concentration of LDL was significantly reduced in patients with active SLE as compared to patients with inactive SLE, RA and NS and to healthy subjects, thereby suggesting that the reduction of PAF acetylhydrolase activity inactive SLE might be due at least in part to a carrier defect related to the activity of the disease.