Myeloperoxidase (MPO) purified from human neutrophils was endocytosed by human monocyte-derived macrophages with a K of uptake of 10.6 nM and a K-d of 27.8 nM. Fucoidan and mannan inhibited the uptake of MPO into the macrophages, indicating that the uptake was mediated by mannose/fucose receptors. Internalized MPO was degraded with a half time of 5.5 h, and the degradation was inhibited by chloroquin. The presence of cytokines during the differentiation of monocytes into macrophages caused enhancement of the endocytosis of MPO by macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin-5 (IL-5), and transforming growth factor-beta (TGF-beta), and inhibition of it by interferon-alpha (IFN-alpha). The stimulatory effect of IFN-gamma or GM-CSF was antagonized by IFN-alpha, but that of TGF-beta was not. In differentiated macrophages, the endocytosis was stimulated by IFN-alpha and TGF-beta, while it was inhibited by IFN-gamma. Expression of the receptor seems to be under multistep control during macrophage differentiation.