A. Aarli et al., SUPPRESSIVE EFFECT ON LYMPHOPROLIFERATION IN-VITRO BY SOLUBLE ANNEXIN-II RELEASED FROM ISOLATED PLACENTAL MEMBRANES, American journal of reproductive immunology [1989], 38(5), 1997, pp. 313-319
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.