Membrane sialoglycolipids regulate the activation of alternative complement pathway by liposomes containing trinitrophenylaminocaproyldipalmitoylphosphatidylethaolamine.
We found that liposomes associated with trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine (TNP-Cap-DDPE) activate the alternative complement pathway (ACP) of guinea-pig. The complement-activating capacity (CAC) of liposomes with TNP-Cap-DPPE (TNP-Cap-liposomes) was found to be inhibited by the insertion of sialoglycolipids such as GM3 onto the membrane. However, neutral glycolipids tested had no inhibitory effect on the CAC of the TNP-Cap-liposomes. The minimum amount of sialoglycolipids required for the inhibition of the ACP-activating capacity of TNP-Cap-liposomes was 0.01 or less in molar ratio to dimyristoylphosphatidylcholine in the liposomes. Since the insertion of charged amphiphiles did not affect the status of TNP-Cap-liposomes containing glycolipids with respect to their ACP-activating capacity, the surface potential caused by sialoglycolipids was disregarded as being the factor responsible for restriction of the complement-activating effect. For the inhibitory effect to be manifested, it was demonstrated that the presence of GM3 was required on the same liposome membrane as where the TNP-Cap-triggered ACP activation is taking place. Therefore, sialoglycolipids may inhibit ACP activation by reacting directly on certain nascently activated complement proteins. However, insertion of GM3 could not inhibit liposome lysis via the classical complement pathway. Furthermore, the presence of antibody reaction significantly reduced the inhibitory capacity of GM3 indicating that natural antibody may be responsible for discriminating between self and heterologous surfaces, thus cancelling the glycolipid-mediated restriction of ACP activation in the case of heterologous cell surface, bringing about lysis by the cancellation of the glycolipid-mediated restriction of ACP activation on heterologous cell surfaces.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D003167:Complement Activation; D003168:Complement Fixation Tests; D003170:Complement Pathway, Alternative; D005679:G(M3) Ganglioside / Q000276:immunology; D006017:Glycolipids / Q000276:immunology*; D006168:Guinea Pigs; D008081:Liposomes / Q000276:immunology*; D008563:Membrane Lipids / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000276:immunology*
D000906:Antibodies; D005679:G(M3) Ganglioside; D006017:Glycolipids; D008081:Liposomes; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; C009255:sialoglycolipids; C033368:N-(2,4,6-trinitrophenyl-6-N-aminocaproyl)-1,2-dipalmitoylphosphatidylethanolamine