Effects of platelet activating factor on calcium-lipid interactions and lateral phase separations in phospholipid vesicles.
Recent studies localizing the inflammatory mediator, platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), to the membranes of stimulated neutrophils, raise the possibility that PAF may, in addition to its activities as a mediator, alter the physical properties of membranes. This, and the increasing evidence that calcium-lipid interactions may have central importance in membrane organizational structure and in functions of cell homeostasis and stimulus-response coupling, prompted us to study the effects of PAF on calcium-lipid interactions in lipid vesicles. Using fluorescence polarization of dansylated probes located in the glycerol portion of the membrane bilayer, PAF (at a concentration as low as 1 mol%) was shown to reduce membrane rigidification significantly during calcium-induced lateral phase separations. This effect of PAF was structurally dependent on both the 1-position alkyl linkage and the 2-position acetyl group as shown by studies of related lipid analogs. Furthermore, using a self-quenching probe, it was shown that inhibition of lateral phase separation did not account for this reduction in the calcium-induced membrane rigidification attributed to PAF. Data suggest that PAF at low concentrations may alter phospholipid head packing and, thereby, change membrane surface features during calcium-lipid interactions, effects which may ultimately explain some of its biological actions.
Bratton
D L
DL
National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Science Center, Denver 80206.
Harris
R A
RA
Clay
K L
KL
Henson
P M
PM
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D003619:Dansyl Compounds; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D005990:Glycerol / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008561:Membrane Fusion / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*
D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D010972:Platelet Activating Factor; C040328:dansylphosphatidylserine; D004161:Diphenylhexatriene; C042077:N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; C056851:N-5-dimethylaminonaphthalene-1-sulfonyl-dipalmitoylphosphatidylethanolamine; D005990:Glycerol; D002118:Calcium