Tuftsin (Thr-Lys-Pro-Arg) is a natural immunomodulating peptide. We ha
ve investigated for the presence of a specific tuftsin receptor on mur
ine Kupffer cells using fluorescein-labeled tuftsin, which retains ful
l biological activity. After incubation with fluorescein-labeled tufts
in, Kupffer cells displayed clear binding of this compound on the plas
ma membrane. Excess tuftsin inhibited this binding, indicating the pre
sence of specific tuftsin receptors on the Kupffer cells. We then inve
stigated the effect of tuftsin on the phagocytic activity of these cel
ls. Phagocytosis assays were performed on 24-well plates between murin
e Kupffer cells and fluorescent microspheres. The greatest stimulatory
effect of tuftsin on percent phagocytic cells over the control value
was observed when the cells were incubated with particles at 1 mug/ml
tuftsin for 15 min at 37-degrees-C with a particle-to-Kupffer cell rat
io of 50:1. Tuftsin also markedly increased the number of particles en
gulfed by Kupffer cells under the same conditions. These results indic
ate that Kupffer cells have specific tuftsin receptors; thus tuftsin c
an stimulate phagocytic activity of Kupffer cells, which constitute th
e majority of macrophages in the host and are situated strategically i
n the liver for host defense.