• Modulation of inflammatory platelet-activating factor (PAF) receptor by the acyl analogue of PAF.

Modulation of inflammatory platelet-activating factor (PAF) receptor by the acyl analogue of PAF.

Journal of lipid research (2018-08-25)
Vyala Hanumanthareddy Chaithra, Shancy Petsel Jacob, Chikkamenahalli Lakshminarayana Lakshmikanth, Mosale Seetharam Sumanth, Kandahalli Venkataranganayaka Abhilasha, Chu-Huang Chen, Anita Thyagarajan, Ravi P Sahu, Jeffery Bryant Travers, Thomas M McIntyre, Kempaiah Kemparaju, Gopal Kedihithlu Marathe

Platelet-activating factor (PAF) is a potent inflammatory mediator that exerts its actions via the single PAF receptor (PAF-R). Cells that biosynthesize alkyl-PAF also make abundant amounts of the less potent PAF analogue acyl-PAF, which competes for PAF-R. Both PAF species are degraded by the plasma form of PAF acetylhydrolase (PAF-AH). We examined whether cogenerated acyl-PAF protects alkyl-PAF from systemic degradation by acting as a sacrificial substrate to enhance inflammatory stimulation or as an inhibitor to dampen PAF-R signaling. In ex vivo experiments both PAF species are prothrombotic in isolation, but acyl-PAF reduced the alkyl-PAF-induced stimulation of human platelets that express canonical PAF-R. In Swiss albino mice, alkyl-PAF causes sudden death, but this effect can also be suppressed by simultaneously administering boluses of acyl-PAF. When PAF-AH levels were incrementally elevated, the protective effect of acyl-PAF on alkyl-PAF-induced death was serially decreased. We conclude that, although acyl-PAF in isolation is mildly proinflammatory, in a pathophysiological setting abundant acyl-PAF suppresses the action of alkyl-PAF. These studies provide evidence for a previously unrecognized role for acyl-PAF as an inflammatory set-point modulator that regulates both PAF-R signaling and hydrolysis.


ギンコリドB Ginkgo biloba(イチョウ)葉由来, ≥90% (HPLC)
Lyso PAF (from Heart PC), Avanti Polar Lipids 840008P, powder