Montenegro Mary Lourdes, Ferriani Rui Alberto, Basse Per H
Department of Gynecology and Obstetrics of Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirao Preto, SP, Brazil.
Department of Immunology of University of Pittsburgh, Pittsburgh, PA, USA.
BMC Immunol. 2015 Aug 29;16:51. doi: 10.1186/s12865-015-0105-0.
Endometriosis is defined as the presence of endometrial glands and stroma at ectopic locations. Although the prevalence of endometriosis is as high as 35%-50%, its pathogenesis remains controversial. An increasing number of studies suggest that changes in immune reactivity may be primarily involved in the development of endometriosis development. In this sense, it has been strongly suggested that a fundamental part of immunologic system, the natural killer cells (NK cells), are an important part of this process. NK cells, a component of the innate immune system, have been extensively studied for their ability to defend the organism against infections and malignancy. Recent studies have shown that IL-2-activated NK (A-NK) cells are able to attack and destroy tumors in lungs and livers of mice, demonstrating the therapeutic potential of these cells. Similarly to metastatic tumor cells, endometrial cells are able to adhere, infiltrate and proliferate at ectopic locations. Therefore, in this study, we evaluated the ability of adoptively transferred and endogenous NK cells to infiltrate endometriosis lesions.
As NK cells donors were used C57BL/6 B6. PL- Thy 1.1 female mice. As uterine horns donors were used C57/BL6+GFP female mice and as endometriosis recipients C57BL/6 Thy1.2 female mice. Endometriosis induction was made by injection of endometrial tissue fragments. After 4 weeks, necessary for endometriosis lesions establishment the animals were divided in 3 experimental groups with 10 animals each. Group 1 received i.v doses of 5x106 A-NK in 200μl RPMI; Group 2 received i.p dose of 5x106 A-NK in 200μl RPMI and Group 3 received i.p dose of IL2 (0.5 mL RPMI containing 5.000U of IL2).
Our data show that exogenous A-NK cells injected via ip combined with endogenous A-NK cells seems to be the most efficient way for activated NK cells track and infiltrate endometriosis.
For the first time, it was shown that both endogenous as exogenous A-NK cells are able to track, migrate and infiltrate endometriosis lesion. This seems to be a promising result, and if confirmed the efficiency of A-NK cells in killing endometriosis lesions, maybe in the future we could use this approach as an alternative treatment for women with endometriosis.
子宫内膜异位症定义为子宫内膜腺体和间质出现在异位部位。尽管子宫内膜异位症的患病率高达35%-50%，但其发病机制仍存在争议。越来越多的研究表明，免疫反应性的改变可能主要参与了子宫内膜异位症的发生发展。从这个意义上讲，强烈提示免疫系统的一个基本组成部分，即自然杀伤细胞（NK细胞），是这一过程的重要组成部分。NK细胞作为固有免疫系统的一个组成部分，因其抵御机体感染和恶性肿瘤的能力而受到广泛研究。最近的研究表明，白细胞介素-2激活的NK（A-NK）细胞能够攻击并破坏小鼠肺和肝脏中的肿瘤，证明了这些细胞的治疗潜力。与转移性肿瘤细胞类似，子宫内膜细胞能够在异位部位黏附、浸润和增殖。因此，在本研究中，我们评估了过继转移的和内源性NK细胞浸润子宫内膜异位症病灶的能力。
使用C57BL/6 B6.PL-Thy 1.1雌性小鼠作为NK细胞供体。使用C57/BL6+GFP雌性小鼠作为子宫角供体，使用C57BL/6 Thy1.2雌性小鼠作为子宫内膜异位症受体。通过注射子宫内膜组织碎片诱导子宫内膜异位症。4周后，即子宫内膜异位症病灶形成所需时间，将动物分为3个实验组，每组10只动物。第1组静脉注射200μl RPMI中含5×10⁶个A-NK细胞；第2组腹腔注射200μl RPMI中含5×10⁶个A-NK细胞，第3组腹腔注射IL2（0.5 mL含5000U IL2的RPMI）。
我们的数据表明，腹腔注射外源性A-NK细胞与内源性A-NK细胞相结合似乎是激活的NK细胞追踪和浸润子宫内膜异位症病灶的最有效方式。
首次表明内源性和外源性A-NK细胞均能够追踪、迁移并浸润子宫内膜异位症病灶。这似乎是一个有前景的结果，如果A-NK细胞杀伤子宫内膜异位症病灶的效率得到证实，也许未来我们可以将这种方法用作子宫内膜异位症女性的替代治疗方法。
