Endometriosis, a disease of the macrophage.
Endometriosis, a disease of the macrophage.
复制标题
DOI：
10.3389/fimmu.2013.00009
复制
发表时间：
2013
影响因子：
7.3
通讯作者：
Rovere-Querini P
中科院分区：
文献类型：
--
作者：
Capobianco A;Rovere-Querini P
子宫内膜异位症是盆腔疼痛和女性不孕的常见原因，它依赖于异位部位血管化子宫内膜组织的生长。子宫内膜碎片在生育期到达腹膜腔：局部线索决定它们是否产生子宫内膜病变。巨噬细胞在缺氧和组织应激的部位被招募，在那里它们清除细胞碎片和血红素铁并产生促生命和促血管生成信号。巨噬细胞在增生性病变中丰富，在那里被募集并经历交替激活。在啮齿类动物中，巨噬细胞是病变建立和生长所必需的;骨髓来源的表达Tie-2的巨噬细胞特异性地促进病变新生血管形成，可能是因为它们与循环内皮祖细胞的募集一致，并维持它们的存活和血管壁的完整性。巨噬细胞感知病变中的线索（缺氧、细胞死亡、铁过载）并做出反应，传递信号以恢复局部稳态：它们的作用代表疾病自然史中必要的、非冗余的步骤。子宫内膜异位症可能是由于巨噬细胞对异位子宫内膜组织的误解。它们将其视为伤口，它们激活导致异位细胞存活和组织血管化的程序。清除这种误解是开发子宫内膜异位症新药物治疗的关键领域，这是一种迫切且未满足的医疗需求。
Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.