Enhancement of chemiluminescence and phagocytic activities by nontoxic and toxic forms of lipid A

The effect on the respiratory burst of murine splenic cells after in vitro exposure to nontoxic monophosphoryl lipid A (MPL), toxic diphosphoryl lipid A (DPL), and refined standard endotoxin (RSE) was studied by luminol-dependent, zymosan-stimulated chemiluminescence (CL). CL was stimulated only to a minimum degree by 0.1 μg of MPL, DPL, or RSE, but this was clearly increased when 10-fold higher doses were used. CL activity generated by RSE, which contains only lipid A and ketodeoxyoctanate, remained at a moderate level, even when 100-fold higher doses were used. In contrast, keto-deoxyoctanate-free DPL elevated CL in a dose-dependent manner. Nontoxic MPL at a high dose significantly enhanced CL generation to levels that were comparable to those stimulated by DPL. In addition, phagocytosis of freshly prepared fluorescent beads by adherent peritoneal macrophages was enhanced seven- to 10-fold by toxic DPL and reference LPS, and fivefold by nontoxic MPL.