Hodson Leigh J, Chua Angela C L, Evdokiou Andreas, Robertson Sarah A, Ingman Wendy V
School of Medicine, University of Adelaide at the Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville, South Australia, Australia.
Biol Reprod. 2013 Sep 19;89(3):65. doi: 10.1095/biolreprod.113.109561. Print 2013 Sep.
The mammary gland undergoes development and regression over the course of the ovarian cycle under the regulation of ovarian hormones. Macrophages are implicated as local mediators of this tissue remodeling and may also affect immune surveillance and tumor incidence. To investigate cycle-related changes in macrophage phenotype, mammary gland cells from naturally cycling Cfms-Gfp mice recovered at estrus, metestrus, diestrus, and proestrus were analyzed by flow cytometry. Macrophage expression of MHCII was highest in the proestrus phase, with a 1.6-fold increase compared to the metestrus phase. Similarly, macrophage expression of CD204 was 1.9-fold higher at proestrus compared to estrus. Conversely, macrophage expression of NKG2D was increased at metestrus and diestrus by 7-fold and 5-fold, respectively, compared to estrus. To investigate hormonal regulation of macrophage phenotype, an ovariectomy and hormone replacement model was utilized. Ovariectomized mice were stimulated with exogenous estradiol and progesterone to induce early alveolar development, then given progesterone receptor antagonist RU486 to elicit alveolar bud regression. Progesterone and estradiol in combination reduced macrophage expression of MHCII and CD204 by 5-fold and 3-fold, respectively, and increased macrophage expression of NKG2D by 4-fold. Administration of RU486, following estradiol and progesterone, reversed the macrophage phenotype. These results reveal an essential requirement for ovarian hormones in regulating macrophage phenotype in the mammary gland and indicate that progesterone is particularly critical for controlling macrophage antigen presentation and immune surveillance capacity.
在卵巢激素的调节下，乳腺在卵巢周期过程中经历发育和退化。巨噬细胞被认为是这种组织重塑的局部介质，并且可能还会影响免疫监视和肿瘤发生率。为了研究巨噬细胞表型与周期相关的变化，通过流式细胞术分析了在动情期、动情后期、间情期和动情前期采集的自然周期Cfms-Gfp小鼠的乳腺细胞。MHCII在巨噬细胞中的表达在动情前期最高，与动情后期相比增加了1.6倍。同样，CD204在巨噬细胞中的表达在动情前期比动情期高1.9倍。相反，与动情期相比，NKG2D在巨噬细胞中的表达在动情后期和间情期分别增加了7倍和5倍。为了研究巨噬细胞表型的激素调节，采用了卵巢切除术和激素替代模型。对去卵巢小鼠用外源性雌二醇和孕酮刺激以诱导早期肺泡发育，然后给予孕酮受体拮抗剂RU486以引发肺泡芽退化。孕酮和雌二醇联合使用分别使MHCII和CD204在巨噬细胞中的表达降低了5倍和3倍，并使NKG2D在巨噬细胞中的表达增加了4倍。在给予雌二醇和孕酮后给予RU486可逆转巨噬细胞表型。这些结果揭示了卵巢激素在调节乳腺巨噬细胞表型中的重要作用，并表明孕酮对于控制巨噬细胞抗原呈递和免疫监视能力尤为关键。
