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

Autor:	Chaithra VH; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Jacob SP; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Lakshmikanth CL; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Sumanth MS; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Abhilasha KV; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Chen CH; Vascular and Medicinal Research, Texas Heart Institute, Houston, TX 77030., Thyagarajan A; Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435., Sahu RP; Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435., Travers JB; Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435., McIntyre TM; Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH., Kemparaju K; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India., Marathe GK; Department of Studies in Biochemistry University of Mysore, Manasagangothri, Mysuru 570006, India marathe1962@gmail.com.; and Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru 570006, India.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2018 Nov; Vol. 59 (11), pp. 2063-2074. Date of Electronic Publication: 2018 Aug 23.
DOI:	10.1194/jlr.M085704
Abstrakt:	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. (Copyright © 2018 Chaithra et al.)
Databáze:	MEDLINE
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