The proinflammatory mediator Platelet Activating Factor is an effective substrate for human group X secreted phospholipase A2.
Platelet Activating Factor (PAF) is a potent mediator of inflammation whose biological activity depends on the acetyl group esterified at the sn-2 position of the molecule. PAF-acetylhydrolase (PAF-AH), a secreted calcium-independent phospholipase A(2), is known to inactivate PAF by formation of lyso-PAF and acetate. However, PAF-AH deficient patients are not susceptible to the biological effects of inhaled PAF in airway inflammation, suggesting that other enzymes may regulate extracellular levels of PAF. We therefore examined the hydrolytic activity of the recently described human group X secreted phospholipase A(2) (hGX sPLA(2)) towards PAF. Among different sPLA(2)s, hGX sPLA(2) has the highest affinity towards phosphatidylcholine (PC), the major phospholipid of cellular membranes and plasma lipoproteins. Our results show that unlike group IIA, group V, and the pancreatic group IB sPLA(2), recombinant hGX sPLA(2) can efficiently hydrolyze PAF. The hydrolysis of PAF by hGX sPLA(2) rises abruptly when the concentration of PAF passes through its critical micelle concentration suggesting that the enzyme undergoes interfacial binding and activation to PAF. In conclusion, our study shows that hGX sPLA(2) may be a novel player in PAF regulation during inflammatory processes.
Gora
Sarah
S
INSERM U525, Université Pierre et Marie Curie-Paris 6, Faculté de Médecine Pierre et Marie Curie, Paris, France.
Lambeau
Gerard
G
Bollinger
James G
JG
Gelb
Michael
M
Ninio
Ewa
E
Karabina
Sonia-Athina
SA
D000818:Animals; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; D006801:Humans; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010741:Phospholipases A / Q000737:chemistry*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013379:Substrate Specificity; D013552:Swine
D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; C516299:PLA2G5 protein, human; D054467:Phospholipases A2