Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptor.
We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.
Nagayama
Susumu
S
Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Ogawara
Ken-ichi
K
Minato
Keiko
K
Fukuoka
Yoshiko
Y
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000327:Adsorption; D000818:Animals; D002478:Cells, Cultured; D008099:Liver / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles; D011137:Polystyrenes / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D051116:Receptors, Scavenger / Q000502:physiology*; D000509:alpha-Fetoproteins / Q000493:pharmacokinetics / Q000502:physiology*
D011137:Polystyrenes; D051116:Receptors, Scavenger; D000509:alpha-Fetoproteins