Enhancement of delayed-type hypersensitivity by bestatin, an inhibitor of aminopeptidase B and leucine aminopeptidase.

Abstract

The effects of bestatin on aminopeptidases on the cell surface and on delayed-type hypersensitivity and immunity to Ehrlich carcinoma are reported. Bestatin ([2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine), inhibits aminopeptidase B and leucine aminopeptidase. Moreover, the compound was found to inhibit the activity of both aminopeptidase B and leucine aminopeptidase on the cell surface. A binding of bestatin with these enzymes on the cell surface was suggested. Further studies revealed that bestatin augmented delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC). Female mice were immunized by injection of 108 SRBC. The specific of the DTH reaction, enhanced by bestatin, was confirmed by comparing SRBC and human red blood cells (group 0) as antigens. Further studies dealt with the effect of bestatin on humoral antibody formation. Bestatin may be useful in cancer therapy.