Analysis of proteases involved in phagocytic activity of macrophages through the use of various amino acid esters.
Inhibitory effects of various amino acid esters on the phagocytic activity of guinea pig peritoneal macrophages were studied with sensitized 51Cr-sheep erythrocytes (51Cr-EAb) as well as 125I-alpha-amylase complexed with homologous IgG2 antibody (Ag-Ab complex). The intracellular uptake of 51Cr-EAb was markedly inhibited by N-acetyl-L-phenylalanine ethyl ester (Ac-Phe-OEt), N-acetyl-L-tryptophan ethyl ester (Ac-Trp-OEt) and N-benzoyl-L-tyrosine ethyl ester (Bz-Tyr-OEt), but not by N-acetyl-L-tyrosine ethyl ester (Ac-Tyr-OEt), N-alpha-acetyl-L-arginine methyl ester (Ac-Arg-OMe), N-alpha-benzoyl-L-arginine ethyl ester (Bz-Arg-OEt) or N-alpha-acetyl-L-lysine methyl ester (Ac-Lys-OMe). When phagocytosis of the Ag-Ab complex was assayed by measuring the amount of digested products released from macrophage cells, Ac-Tyr-OEt also inhibited it as markedly as Ac-Phe-OEt, Ac-Trp-OEt, and Bz-Tyr-OEt did, whereas Bz-Arg-OEt again did not show any effect. The results of analysis of the intracellular fate of the Ag-Ab complex taken up by macrophages through the use of analytical density gradient fractionation of the homogenized cells suggest that Ac-Phe-OEt inhibits the ingestive process since the distribution of Ag-Ab complex showed a single peak, closely accompanying the plasma membrane. Ac-Tyr-OEt, on the other hand, caused a marked accumulation of Ag-Ab complex in the lysosome fraction, reflecting the inhibition of intralysosomal digestion of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D004912:Erythrocytes / Q000276:immunology; D006168:Guinea Pigs; D008264:Macrophages / Q000276:immunology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D012756:Sheep
D000596:Amino Acids; D010447:Peptide Hydrolases