Mast cell regulation of human endometrial matrix metalloproteinases: A mechanism underlying menstruation.
Mast cell regulation of human endometrial matrix metalloproteinases: A mechanism underlying menstruation.
复制标题
肥大细胞对人子宫内膜基质金属蛋白酶的调节：月经的机制。
DOI：
10.1095/biolreprod59.3.693
复制
发表时间：
1998
影响因子：
3.6
通讯作者：
Salamonsen,LA
中科院分区：
文献类型：
--
作者：
Zhang,J;Nie,G;Jian,W;Woolley,DE;Salamonsen,LA
子宫内膜基质金属蛋白酶（MMPs）在月经期间急剧增加，据称会导致月经期间局灶性组织破坏，但其表达或激活如何受到局部调节尚不清楚。肥大细胞激活发生在月经周围子宫内膜，我们假设肥大细胞产物会调节子宫内膜MMPs。我们研究了人类肥大细胞和子宫内膜间质细胞在MMP产生和激活方面的相互作用。人肥大细胞系（HMC-1）与基质细胞共培养，刺激基质细胞proMMP-1和proMMP-3的产生，并在较小程度上刺激proMMP-2的产生，随着肥大细胞数量的增加而增加。肥大细胞条件培养基也增加了基质中proMMP-1和proMMP-3的蛋白和mRNA，但这被抗血清对白细胞介素-1和肿瘤坏死因子α的预吸附所消除。将肥大细胞条件培养基添加到基质细胞培养基中，并添加肝素（稳定胰蛋白酶活性），导致MMP-3和MMP-1活性的分子量形式出现。因此，月经前子宫内膜内激活的肥大细胞有可能刺激子宫内膜基质细胞产生MMP并启动前体激活，这可能解释了子宫内膜MMP作用的局部性质，导致月经时组织的局部破坏。
Endometrial matrix metalloproteinases (MMPs), which increase dramatically at menstruation, are purported to cause the focal tissue breakdown at menstruation, but how their expression or activation is locally regulated is unknown. Mast cell activation occurs within perimenstrual endometrium, and we postulated that mast cell products would regulate endometrial MMPs. We have examined the interaction between human mast cells and endometrial stromal cells with regard to MMP production and activation. The human mast cell line (HMC-1) in coculture with stromal cells stimulated stromal cell proMMP-1 and proMMP-3, and to a lesser extent proMMP-2 production, with increasing stimulation as mast cell number increased. Mast cell-conditioned medium also increased both protein and mRNA for stromal proMMP-1 and proMMP-3, this being abrogated by preadsorption of mast cell-conditioned medium with antisera to interleukin-1 and tumor necrosis factor α. Mast cell-conditioned medium added to stromal cell culture medium in vitro along with added heparin (which stabilizes tryptase activity) resulted in the appearance of molecular weight forms indicative of active MMP-3 and MMP-1. Thus activated mast cells within the endometrium prior to menstruation have the potential to stimulate MMP production by endometrial stromal cells and to initiate precursor activation, and are likely to account for the local nature of endometrial MMP action resulting in foci of tissue breakdown at menstruation.