Phospholipid bilayers enhance the stability of leukotriene A4 and epoxytetraenes: stabilization of eicosanoids by liposomes.
The hydrolysis of leukotriene A4 and two epoxytetraenes was examined in the presence and absence of liposomes. When added to liposomes in suspension, the stability of LTA4 was increased in a time- and dose-dependent fashion. At 10 min, the half-life of LTA4 was increased 67.1 +/- 6.8% in the presence of liposomes which was comparable to that observed with albumin (10 mg/ml): 68.3 +/- 6.9%. Phosphatidylcholine, in a non-bilayer configuration, was also effective in enhancing the half-life of LTA4, albeit to a lesser extent than liposomes. At equal molar concentrations, the enhanced stability of eicosanoid epoxides with liposomes gave a rank order with leukotriene A4 greater than 5(6)epoxytetraene greater than 14(15)epoxytetraene. Results indicate that phospholipid bilayers can protect leukotriene A4 and 5(6)epoxytetraene from non-enzymatic hydrolysis. Moreover, they suggest that the biological half-life of intermediates involved in the formation of both leukotrienes and lipoxins can be increased by their association with membranes.
Fiore
S
S
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Serhan
C N
CN
D000418:Albumins; D004355:Drug Stability; D015118:Eicosapentaenoic Acid; D006207:Half-Life; D006801:Humans; D017572:Leukotriene A4; D015289:Leukotrienes; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids
D000418:Albumins; D017572:Leukotriene A4; D015289:Leukotrienes; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; D015118:Eicosapentaenoic Acid