In-vitro studies of the potential role of neutrophils in the process of menstruation
In-vitro studies of the potential role of neutrophils in the process of menstruation
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DOI：
10.1093/molehr/6.10.899
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发表时间：
2000-10-01
影响因子：
4
通讯作者：
Salamonsen, LA
中科院分区：
文献类型：
--
作者：
Lathbury, LJ;Salamonsen, LA
大量的中性粒细胞仅在月经周期的经前期和月经期在子宫内膜血管外发现。在这项研究中，我们研究了中性粒细胞产物对基质金属蛋白酶（MMP）的合成和活化的影响，MMP被认为在月经期间发生的子宫内膜组织降解中起着至关重要的作用。子宫内膜间质成纤维细胞和外周血中性粒细胞共同培养时，其分泌的MMP-2、MMP-3和MMP-9被激活。金属蛋白酶组织抑制剂（TIMP）1和2也在该系统中降解。中和研究确定了丝氨酸蛋白酶弹性蛋白酶在观察到的MMP活化中的作用。虽然培养的子宫内膜中性粒细胞的行为类似于外周血中性粒细胞的能力，释放潜在的MMP-9和弹性蛋白酶，没有活性形式的MMP-2。MMP-3和MMP-9在含有子宫内膜中性粒细胞和间质成纤维细胞的共培养物的上清液中检测到。这似乎是由于在这些培养物中中性粒细胞产生弹性蛋白酶和抑制剂（例如α 1-抗胰蛋白酶）的改变，使得活性弹性蛋白酶不可用。我们的研究结果表明，中性粒细胞在月经时发生的组织破坏的任何参与可能受到降解酶及其各自抑制剂的焦点浓度的严格调节。
Significant numbers of neutrophils are found extravascularly within the endometrium only during the immediate premenstrual and menstrual phases of the cycle. In this study we investigated the effect of neutrophil products on the synthesis and activation of matrix metalloproteinases (MMP), enzymes considered to play a crucial role in the degradation of endometrial tissue that occurs at menstruation. Latent MMP-2, MMP-3 and MMP-9 released by endometrial stromal fibroblasts and peripheral blood neutrophils were activated when the two cell types were cultured together. Tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were also degraded in this system. Neutralization studies identified a role for the serine protease, elastase, in the observed activation of MMP. Although cultured endometrial neutrophils behaved similarly to peripheral blood neutrophils in their ability to release latent MMP-9 and elastase, no active forms of MMP-2. MMP-3 and MMP-9 were detected in supernatant from co-cultures containing endometrial neutrophils and stromal fibroblasts. This appeared to be due to an alteration in the neutrophil production of elastase and inhibitors, e.g. alpha 1-antitrypsin, in these cultures so that active elastase was not available. Our results demonstrate that any involvement of neutrophils in the tissue destruction occurring at menstruation may be tightly regulated by the focal concentration of degradative enzymes and their respective inhibitors.