Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1.
The mode of action of immunological adjuvants is not yet completely understood. Many are particulate. Certain antigen-presenting (dendritic) cell populations belong to the monocyte/macrophage lineage and, like other members of the lineage, in some tissues appear to be short-lived. We report that many poorly degradable, particulate adjuvants, for example, aluminum hydroxide, oil-in-water emulsions, calcium phosphate, and silica, enhance murine bone marrow-derived macrophage survival; induction of DNA synthesis was even observed. No evidence could be found for a requirement for endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage-CSF (M-CSF or CSF-1). Synergy for the proliferative effects was noted in the presence of added GM-CSF or CSF-1. It is suggested from these in vitro findings that one function of certain particulate adjuvants may be to increase by enhanced survival or even proliferation the number of cells available for subsequent antigen presentation and cytokine production.
Hamilton
J A
JA
Inflammation Research Centre, University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia. j.hamilton@medicine.unimelb.edu.au
Byrne
R
R
Whitty
G
G
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D004655:Emulsions / Q000494:pharmacology; D004705:Endocytosis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008297:Male; D008351:Mannans / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010710:Phosphates / Q000494:pharmacology; D062605:Quillaja Saponins; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology; D013185:Squalene / Q000737:chemistry / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D002130:Calcium Phosphates; D004655:Emulsions; D008351:Mannans; D010710:Phosphates; D062605:Quillaja Saponins; D012503:Saponins; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D000536:Aluminum Hydroxide; C046386:Quil A; C485838:calcium phosphate, monobasic, anhydrous; D013185:Squalene; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C020243:calcium phosphate; C012714:aluminum phosphate; C485829:calcium phosphate, dibasic, anhydrous