Plasma PAF-acetylhydrolase: an unfulfilled promise?
Plasma Platelet-activating-Factor (PAF)-acetylhydrolase (PAF-AH also named lipoprotein-PLA(2) or PLA(2)G7 gene) is secreted by macrophages, it degrades PAF and oxidation products of phosphatidylcholine produced upon LDL oxidation and/or oxidative stress, and thus is considered as a potentially anti-inflammatory enzyme. Cloning of PAF-AH has sustained tremendous promises towards the use of PAF-AH recombinant protein in clinical situations. The reason for that stems from the numerous animal models of inflammation, atherosclerosis or sepsis, where raising the levels of circulating PAF-AH either through recombinant protein infusion or through the adenoviral gene transfer showed to be beneficial. Unfortunately, neither in human asthma nor in sepsis the recombinant PAF-AH showed sufficient efficacy. One of the most challenging questions nowadays is as to whether PAF-AH is pro- or anti-atherogenic in humans, as PAF-AH may possess a dual pro- and anti-inflammatory role, depending on the concentration and the availability of potential substrates. It is equally possible that the plasma level of PAF-AH is a diagnostic marker of ongoing atherosclerosis.
Karabina
Sonia-Athina
SA
INSERM U525, Université Pierre et Marie Curie-Paris6, Faculté de Médecine Pierre et Marie Curie, 91, bd de l'Hôpital 75634 Paris cedex 13, France.
Ninio
Ewa
E
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy / Q000201:enzymology
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase