Stimulation of human monocytes by endotoxin-associated protein: inhibition of programmed cell death (apoptosis) and potential significance in adjuvanticity.
Mononuclear phagocytes are essential for adjuvant activity and polyclonal immunoglobulin synthesis induced by endotoxin-associated protein (EP) from Salmonella spp. To define the mechanisms of EP-mediated immunostimulation, we evaluated monocyte functions central to adjuvanticity following exposure to Salmonella typhimurium EP. In this study, we show that EP promotes the survival of monocytes by blocking programmed cell death (apoptosis), enhancing the production of the immunostimulatory cytokine interleukin-1 (IL-1) and stimulating the increased expression of HLA-DR and IL-2 receptors, which are cell membrane proteins that facilitate antigen presentation and IL-2 regulation, respectively. These results indicate that, like lipopolysaccharide, EP is a potent activator of human monocytes and suggest that EP-induced immunostimulation may be mediated, in part, by enhanced monocyte survival, cytokine release, and receptor expression.
Mangan
D F
DF
Cellular Immunology Section, National Institute of Dental Research, Bethesda, Maryland 20892.
Wahl
S M
SM
Sultzer
B M
BM
Mergenhagen
S E
SE
D001426:Bacterial Proteins / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008050:Lipid A / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012486:Salmonella typhimurium / Q000276:immunology*; D015854:Up-Regulation
D001426:Bacterial Proteins; D004731:Endotoxins; D006684:HLA-DR Antigens; D007375:Interleukin-1; D008050:Lipid A; D015375:Receptors, Interleukin-2; C027315:lipid A-associated protein, Bacteria