Immunoregulatory activities of human trophoblasts mediated by polyamine complexes

In a previous publication we described the presence in human placenta (HP) of immunosuppressive factors inhibiting the lymphoproliferative responses to mitogen. The results of further study reported herein indicate that the substance involved is of a syncytiotrophoblastic origin, that it is thermostable to 100 degrees C for 1 hr, and of low molecular weight, i.e. 3,500. It was defined as a polyamine conjugate with nucleic acids. Trophoblast cell extracts lost their immunosuppressive ability after heating in cultures of human lymphocytes supplemented with 5% autologous serum. These effects were, however, preserved both in cultures assayed in 5% fetal calf serum and in those to which purified polyamine oxidase (PAO) was added to autologous serum. Trophoblast cell extract was found to contain polyamine oxidases. Placental PAO can be inhibited by quinacrine a typical inhibitor of flavoprotein enzymes but not by isoniazid, an inhibitor of pyridoxal enzymes; this would suggest that the enzymes in human placenta are of a tissular rather than seric origin. The implication of these observations is that immunosuppression is mediated by oxidative products issued from an interaction between polyamine and polyamine oxidase in the syncytiotrophoblast cytosol. This interaction may constitute the basis for a local immunological barrier and may be involved in the protection of the fetus against maternal immune rejection.