Prostaglandin and thromboxane in liposomes: suppression of the primary immune response to liposomal antigens.
Liposomes containing lipid A as adjuvant and also containing prostaglandin E2 or thromboxane B2 were examined for the ability to influence induction of humoral immunity against liposomal protein or lipid antigens in rabbits. The protein antigen consisted of cholera toxin that was bound to ganglioside GM1 on the surface of the liposomes. High titers of anti-cholera toxin antibodies were produced and IgM and IgG responses were detected. When the immunizing liposomes contained either prostaglandin E2 or thromboxane B2 as part of the lipid bilayer, the primary immune response, involving both IgM and IgG antibodies, was greatly reduced. The secondary immune response observed after a boosting immunization was not suppressed by liposomal eicosanoids. A similar inhibitory effect on the primary response was observed when liposomal lipid antigens were examined instead of cholera toxin. An inhibitory effect of liposomal prostaglandin E2 on the phagocytic uptake of opsonized liposomes by cultured macrophages was also observed, suggesting that liposomal eicosanoids can have direct local effects on macrophages that might influence the immune response to liposomal antigens.
Wassef
N M
NM
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Richards
R L
RL
Hayre
M D
MD
Alving
C R
CR
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D003165:Complement System Proteins; D015232:Dinoprostone / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D010587:Phagocytosis; D011817:Rabbits; D013929:Thromboxane B2 / Q000494:pharmacology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008051:Lipid Bilayers; D008081:Liposomes; D013929:Thromboxane B2; D003165:Complement System Proteins; D002772:Cholera Toxin; D015232:Dinoprostone