Inhibition of Lymphocyte Proliferation by Polyamines Requires Ruminant-Plasma Polyamine Oxidase

Abstract

Spermine and spermidine in vitro are potent inhibitors of proliferation of phytohemagglutinin-stimulated rat thymic lymphocytes, lymphoma cells and human lymphoblastic leukemia cells, but only in media supplemented by fetal calf serum. This inhibition was due to a bovine plasma polyamine oxidase, with a high specificity for these polyamines. Spontaneously dividing lymphocytes are not subject to this inhibition. This, plus direct evidence from synchronous cultures of [human Burkitt lymphoma] EB2 cells demonstrated that the inhibition is expressed in the late G1 or G1/S interface of the cell cycle. Putrescine was not an inhibitor in the presence of fetal calf serum but became so in the presence of human pregnancy serum, possibly due to the action of diamine oxidase.