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Immunomodulation with liposomes: the immune response elicited by liposomes with entrapped
Abstract:
Macrophages in the murine spleen were eliminated by the intravenous administration of dichloromethylene-diphosphonate (DMDP) encapsulated in liposomes. The immune response against an antigen (bovine serum albumin, BSA) or hapten (dinitrophenyl, DNP) associated with the surface of the DMDP liposomes was studied. Significant effects of macrophage elimination on the primary (IgM), but not on the secondary (IgG), anti-BSA response were found. Dramatic effects on the response against liposome-associated DNP were observed in macrophage-depleted mice. The number of anti-DNP antibody-forming cells in the spleen decreased from 300 to 28 per section, and anti-DNP serum titres dropped to 12% of their normal values. Since a similar phenomenon was observed for TNP-Ficoll, a thymus-independent type-2 antigen (and not for thymus-dependent or thymus-independent type-1 antigens), we suggest that this response should be classified as thymus-independent type-2 on grounds of its in vivo behaviour. We conclude that adjuvant activity (and memory formation) of liposomes with antigen exposed on their surface occurs irrespective of the presence or absence of splenic macrophages, and that DMDP liposomes could be useful in drug targeting with antigenic liposomes.
Insights
Eliminating splenic macrophages with dichloromethylene-diphosphonate (DMDP) liposomes impacted immune responses. While primary anti-BSA responses were affected, responses to liposome-associated dinitrophenyl (DNP) were dramatically reduced, suggesting a thymus-independent type-2 classification.
Area of Science:
- Immunology
- Liposome Technology
- Drug Delivery
Background:
- Macrophages play a critical role in immune responses.
- Liposomes are versatile carriers for antigens and drugs.
- Understanding macrophage roles in adaptive immunity is crucial for vaccine development.
Purpose of the Study:
- To investigate the role of splenic macrophages in immune responses to liposome-associated antigens.
- To characterize the immune response against bovine serum albumin (BSA) and dinitrophenyl (DNP) on dichloromethylene-diphosphonate (DMDP)-encapsulated liposomes.
- To determine the adjuvant activity and memory formation of liposomes in the absence of splenic macrophages.
Main Methods:
- Selective elimination of splenic macrophages using DMDP-encapsulated liposomes in mice.
- Assessment of primary (IgM) and secondary (IgG) antibody responses to BSA.
- Evaluation of immune responses to liposome-associated DNP, including antibody-forming cells and serum titers.
- Classification of antigen response based on thymus-dependency.
Main Results:
- Macrophage depletion significantly affected primary anti-BSA IgM responses but not secondary IgG responses.
- A dramatic reduction in anti-DNP antibody-forming cells and serum titers was observed in macrophage-depleted mice.
- The observed immune response to liposome-associated DNP mirrored that of thymus-independent type-2 antigens.
Conclusions:
- Splenic macrophages are crucial for effective immune responses to certain liposome-associated antigens, particularly thymus-independent type-2 antigens.
- Liposome adjuvant activity and memory formation can occur independently of splenic macrophages.
- DMDP-liposomes with exposed antigens show potential for targeted drug delivery and immunomodulation.