Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids.
Lysophosphatidylcholine is an abundant component of plasma and oxidized LDL that displays several biological activities, some of which may occur through the platelet-activating factor (PAF) receptor. We find that commercial lysophosphatidylcholine, its alkyl homolog (lyso-PAF), and PAF all induce inflammation in a murine model of pleurisy. Hydrolysis of PAF to lyso-PAF by recombinant PAF acetylhydrolase abolished this eosinophilic infiltration, implying that lyso-PAF should not have displayed inflammatory activity. Saponification of lyso-PAF or PAF acetylhydrolase treatment of lyso-PAF or lysophosphatidylcholine abolished activity; neither lysolipid should contain susceptible sn-2 residues, suggesting contaminants account for the bioactivity. Lyso-PAF and to a lesser extent lysophosphatidylcholine stimulated Ca(2+) accumulation in 293 cells stably transfected with the human PAF receptor, and this was inhibited by specific PAF receptor antagonists. Again, treatment of lyso-PAF or lysophosphatidylcholine with recombinant PAF acetylhydrolase, a nonselective phospholipase A(2), or saponification of lyso-PAF destroyed the PAF-like activity, a result incompatible with lyso-PAF or lysophosphatidylcholine being the actual agonist. We conclude that neither lyso-PAF nor lysophosphatidylcholine is a PAF receptor agonist, nor are they inflammatory by themselves. We suggest that PAF or a PAF-like mimetic accounts for inflammatory effects of lysophosphatidylcholine and lyso-PAF.
Marathe
G K
GK
Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
Silva
A R
AR
de Castro Faria Neto
H C
HC
Tjoelker
L W
LW
Prescott
S M
SM
Zimmerman
G A
GA
McIntyre
T M
TM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004340:Drug Contamination; D005453:Fluorescence; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation / Q000139:chemically induced*; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010998:Pleurisy / Q000139:chemically induced; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D008244:Lysophosphatidylcholines; C029271:O-deacetyl platelet activating factor; D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C039351:platelet activating factor receptor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002118:Calcium