Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1

Abstract

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. J. Leukoc. Biol. 67: 226-232; 2000.

The efficacy of CpG oligodinucleotides, in combination with conventional adjuvants, as immunological adjuvants to swine streptococcic septicemia vaccine in piglets in vivo

“…The depot effect is considered an important feature by trapping the antigen at the site of administration and by attracting various kinds of cells, including APC and macrophages [45]. Both alum and oil-based emulsions can be efficiently endocytosed by APC eventually leading to an enhanced proliferative response of macrophages and other cells [46]. Whereas alum results in a moderate depot effect, oil emulsions generate a more pronounced depot [45].…”

Generation of improved mucosal vaccines by induction of innate immunity

“…A deposit is formed on injection of alum into tissue, leading to tissue damage, phagocytosis by antigen-presenting cells and possibly the release of danger signals [140]. Furthermore, it has been shown that phagocytosed alum increases the survival of macrophages [141]. Similar fi ndings were found with a number of other particulate adjuvants, including oil-inwater emulsions and calcium phosphate, suggesting that this process may contribute to the effi cacy of particulate adjuvants.…”

Low dose metal particles can induce monocyte/macrophage survival

“…TiAlV and CoCr particle-treated BMM were larger and more vacuolated than untreated cells and contained particles. When BMM were treated with particles in the presence of suboptimal CSF-1 concentrations, 23 an additive effect was seen (data not shown).…”

“…We showed that a number of poorly degradable particulates have a prosurvival activity on monocytes/ macrophages [22][23][24][25][26] ; metallic wear debris can now be added to this list. With regards to mechanism, we recently implicated the antiapoptotic protein Bcl-2 in the prosurvival activity of one of these other particulates.…”

“…CSF-1 blockade can have significant benefit in inflammation/autoimmunity, [16][17][18] and has been implicated in periprosthetic osteolysis. [19][20][21] We previously showed that poorly degradable particulates, including oxidized low-density lipoprotein, 22 adjuvants, 23 inflammatory microcrystals, 24 talc, 24 and b-amyloid and prion protein fibrillogenic peptides, 25 can promote monocyte/macrophage survival in vitro. This prosurvival response might lead to increased macrophage numbers at a site of inflammation or an immune reaction.…”