Role of in vivo scavenger function of macrophages in priming for endogenous production of tumor necrosis factor.

The effects of systemic administrations of immune complex, complement activators, and insoluble particles on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay. Intravenous injection of IgG-opsonized sheep red blood cells (10(8)/mouse) enhanced OK-432-triggered TNF production significantly. This effect was maximal (about 30-fold enhancement) 1.5 to 3 h after the injection and disappeared within 10 h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6 h after its i.v. injection, its effect lasting for 10 h, and disappearing within 24 h. Heat-aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production. The enhancement by latex beads (2 microliters volume of solid/mouse) was maximal (about 60-fold) 3 to 6 h after their i.v. injection, was sustained for at least 20 h, and disappeared within 48 h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.