SUPPRESSIVE EFFECT ON LYMPHOPROLIFERATION IN-VITRO BY SOLUBLE ANNEXIN-II RELEASED FROM ISOLATED PLACENTAL MEMBRANES

PROBLEM: Syncytiotrophoblast microvillous plasma membranes (StMPM) are potent suppressors of lymphoproliferation in vitro. We have previousl y shown that soluble annexin II (AII) is present at higher levels in r etroplacental serum (RPS) than in peripheral serum, and that soluble A LI has an immunosuppressive effect. The aims of this study were to det ermine whether AII can be released from StMPM and whether soluble AII from StMPM exerts any immunosuppressive effect. METHOD OF STUDY: Isola ted StMPM were incubated in growth medium for 18 hr and supernatants w ere prepared by ultracentrifugation. Soluble AII was detected by immun oblotting. StMPM, StMPM supernatant, and affinity-purified AII were an alysed in a lymphoproliferation assay for immunomodulating activity. R ESULTS: AII heavy chain and its pll light chain were detected both in StMPM supernatant and in RPS after removal of StMPM particles by ultra centrifugation. StMPM, StMPM supernatant, and purified AII suppressed lymphoproliferation in a dose-dependent manner. Absorption of AII from StMPM supernatant reduced the suppressive activity. The suppressive e ffect of StMPM supernatant and purified AII was completely reversed by heating at 100 degrees C for 30 min or by adding recombinant interleu kin-2 at 100 units/ml. Although StMPM and affinity-purified AII suppre ssed the proliferation of lymphocytes from all donors tested, StMPM su pernatant suppressed the proliferation of lymphocytes from 12 of 23 do nors. Six of eight female non-suppressed donors were multiparae, where as five of five female suppressed donors were nulliparae. CONCLUSIONS: Annexin II is released by isolated placental membranes in vitro and i s present in RPS, indicating in vivo release of AII at the fetomaterna l interface, probably as AII heterotetramer. AII has immunosuppressive activity and may be important in fetal allograft survival.