MOUSE GRANULATED METRIAL GLAND-CELLS ORIGINATE BY LOCAL ACTIVATION OF UTERINE NATURAL-KILLER LYMPHOCYTES
MOUSE GRANULATED METRIAL GLAND-CELLS ORIGINATE BY LOCAL ACTIVATION OF UTERINE NATURAL-KILLER LYMPHOCYTES
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DOI：
10.1095/biolreprod44.5.834
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发表时间：
1991-05-01
影响因子：
3.6
通讯作者：
YOUNG, JDE
中科院分区：
文献类型：
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作者：
PARR, EL;PARR, MB;YOUNG, JDE
通过对小鼠子宫表面膜标志物LGL-1的免疫染色，鉴定了小鼠子宫内的NK细胞。从交配前到怀孕第14天，这些细胞大量存在。双免疫染色显示子宫NK细胞在妊娠第6天开始含有成孔蛋白穿孔素。穿孔素是一种可能的细胞毒性介质，存在于淋巴因子激活的NK细胞和细胞毒性T淋巴细胞中。妊娠第8天和第10天蜕膜中NK细胞继续激活产生穿孔素，妊娠第12天和第14天子宫内膜腺（mg）外周部分NK细胞同时存在3个激活阶段：小细胞表面有明亮的LGL-1膜染色，但没有穿孔素（未活化），大细胞两种标记物均有中间染色（部分活化），大细胞有明亮的穿孔素染色，但没有LGL-1（完全活化）。这些观察结果表明，随着穿孔素在细胞质中的积累，子宫NK细胞的激活涉及到LGL-1膜的丢失，激活区在怀孕第11天左右从蜕膜转移到MG，非激活的NK细胞可能在此期间不断进入激活区。静止NK细胞可能通过增殖和/或从子宫其他区域迁移而不是从血液中进入活化区，因为在怀孕期间用NK-1.1或asialo GM1抗体处理循环NK细胞对妊娠后期子宫中lgl -1或穿孔阳性细胞的数量没有影响或只有很小的影响。子宫NK细胞可能未被白细胞介素-2 （IL-2）激活，因为子宫内很少有T淋巴细胞存在，此时子宫内也未检测到干扰素。第6天蜕膜外和第8天着床部位之间的NK细胞不含穿孔素，表明激活涉及着床部位产生的局部因子。由于穿孔素先前已被证明存在于小鼠颗粒状子宫腺（GMG）细胞中，我们的观察表明，GMG细胞起源于子宫NK细胞的局部活化，并且GMG细胞可以被识别为活化的NK细胞。
Natural killer (NK) lymphocytes were identified in the mouse uterus by immunostaining their surface membrane marker, LGL-1. The cells were present in large numbers from before mating through Day 14 of pregnancy. Double immunostaining indicated that uterine NK cells began to contain the pore-forming protein, perforin, on Day 6 of pregnancy in mesometrial decidua. Perforin is a probable mediator of cellular cytotoxicity found in lymphokine-activated NK and cytotoxic T lymphocytes. Activation of NK cells to produce perforin continued in mesometrial decidua on Days 8 and 10 of pregnancy and in the peripheral portion of metrial glands (MGs) on Days 12 and 14 of pregnancy, where cells at 3 stages of activation were simultaneously present: small cells with bright surface membrane staining of LGL-1 but no perforin (nonactivated), larger cells with intermediate staining of both markers (partially activated), and large cells with bright staining of perforin but no LGL-1 (fully activated). These observations indicate that activation of uterine NK cells involves loss of membrane LGL-1 as perforin accumulates in the cytoplasm, that the zone of activation shifts from mesometrial decidua to the MG on about Day 11 of pregnancy, and that nonactivated NK cells probably enter activation zones continuously during this period. Resting NK cells may enter activation zones by proliferation and/or migration from other regions of the uterus, rather than from blood, because depletion of circulating NK cells during pregnancy by treatment with NK-1.1 or asialo GM1 antibodies had no effect or only a small effect on the numbers of LGL-1-or perforin-positive cells seen in the uterus later in pregnancy.Uterine NK cells are probably not activated by interleukin-2 (IL-2) since few T lymphocytes were present in the uterus, nor were interferons detected in the uterus at this time. NK cells outside the mesometrial decidua on Day 6 and between implantation sites on Day 8 did not contain perforin, indicating that activation involves local factors produced at implantation sites. Since perforin has previously been shown to be present in mouse granulated metrial gland (GMG) cells, our observations indicate that GMG cells originate by local activation of uterine NK cells and that GMG cells can be identified as activated NK cells.