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J. Biochem, 1986, Vol. 99, No. 5 1317-1326
© 1986 Japanese Biochemical Society

research-article

Inhibitory Effects of Various Synthetic Substrates for Aminopeptidases on Phagocytosis of Immune Complexes by Macrophages1

Sachiko IWAKI, Tohoru NAKAMURA and Jiro KOYAMA

Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences Hokkaido University, kita-ku, Sapporo, Hokkaido 060

The inhibitory effects of various 7-(aminoacyl)-4-methylcoumarinylamides (AA-MCA's), synthetic substrates for aminopeptidases, on phagocytosis of immune complexes by guinea pig peritoneal macrophages were investigated by measuring the intracellular uptake of sensitized 51Cr-sheep erythrocytes and 125[-{alpha}-amylase complexed with homologous IgG2 antibody. Among the AA-MCA's examined, MCA compounds of hydrophobic amino acids (Phe, Tyr, Leu, and Pro) were found to inhibit the intracellular uptake and digestion of immune complexes. Sucrose density gradient centrifugation of the homogenates of macrophages treated with the in hibitors for 1 h at 37°C showed that they modulated the lysosomes, resulting in a decrease in buoyant density of the organella. These effects of the inhibitors on the buoyant density of the lysosomes as well as on the phagocytic activity of macrophages disappeared upon removal of the inhibitors from the cells by washing. Since none of 7-amino-4-methylcoumarin, L-phenylalanine, and bestatin methyl ester could significantly inhibit the phagocytosis of immune complexes by macrophages, the MCA compounds of hydrophobic amino acids appear to inhibit the phagocytosis as a consequence of their lysosomotropic nature.

1This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.


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