Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages.
Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related to the amount of liposomal antigen added per macrophage in the culture medium. At high cell densities, poor presentation occurred when liposomes lacked lipid A but excellent presentation occurred when the liposomes contained lipid A. Liposomes containing lipid A and encapsulated antigen also activated gamma interferon-treated macrophages to produce nitric oxide. Macrophage activation and antigen presentation occurred with liposomes that could not be detected by the Limulus amebocyte lysis assay. Intraperitoneal injection of liposomal lipid A caused a marked increase in the recruitment of immature (peroxidase-positive) macrophages to the peritoneum. On the basis of these experiments, we propose that the mechanism of the adjuvant action of liposomal lipid A is partly due to increased antigen presentation by macrophages and partly due to recruitment of an increased number of macrophages serving as antigen-presenting cells.
Verma
J N
JN
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Rao
M
M
Amselem
S
S
Krzych
U
U
Alving
C R
CR
Green
S J
SJ
Wassef
N M
NM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D000953:Antigens, Protozoan / Q000276:immunology; D007249:Inflammation / Q000473:pathology; D008050:Lipid A / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects; D010961:Plasmodium / Q000276:immunology
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D008050:Lipid A; D008081:Liposomes