Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase.
Platelet-activating factor (PAF) is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation.
Castro Faria Neto
Hugo C
HC
Laboratório de Imunofarmacologia, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
Stafforini
Diana M
DM
Prescott
Stephen M
SM
Zimmerman
Guy A
GA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000737:chemistry / Q000502:physiology*; D011110:Polymorphism, Genetic
D010972:Platelet Activating Factor; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase