The Involvement of the Chemokine RANTES in Regulating Luminal Acidification in Rat Epididymis.
The Involvement of the Chemokine RANTES in Regulating Luminal Acidification in Rat Epididymis.
复制标题
趋化因子 RANTES 参与调节大鼠附睾管腔酸化
DOI：
10.3389/fimmu.2020.583274
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Feng X;Ma BF;Liu B;Ding P;Wei JH;Cheng P;Li SY;Chen DX;Sun ZJ;Li Z
上皮中不同细胞类型之间的复杂相互作用导致附睾腔酸化能力的激活，这一过程对精子的成熟和储存至关重要。基底细胞感知腔内血管紧张素II （ANG II）并通过一氧化氮（NO）刺激透明细胞的质子分泌。我们前期的研究表明，在人附睾F4/80阳性巨噬细胞中表达了激活正常t细胞表达和分泌的趋化因子（RANTES）。本研究的目的是探讨RANTES在调节大鼠附睾腔酸化中的作用。通过体内灌注重组RANTES、Met-RANTES和不同pH值的PBS来研究RANTES的作用。采用输精管切除术改变大鼠附睾管腔ph，用RIA测定组织匀浆ANG II浓度。采用Real - time-PCR和western blot检测附睾组织中AGTR2、RANTES、CCR1、CCR5和iNOS的表达水平。RANTES局限于附睾管基底巨噬细胞，并与其受体CCR1和CCR5共定位。重组RANTES灌注后，附睾尾V-ATPase和iNOS均上调，而拮抗剂Met-RANTES灌注后，透明细胞顶膜V-ATPase和巨噬细胞iNOS的表达上调被完全消除。碱性灌注后，RANTES表达显著升高，并诱导附睾尾部透明细胞中v - atp酶的顶端积累。输精管结扎后附睾尾管腔pH值升高。输精管结扎后附睾尾区ANGⅱ浓度及AGTR2、RANTES、CCR1、CCR5、iNOS表达水平下降。在基底细胞活化后，RANTES可能通过与其受体的相互作用诱导巨噬细胞释放NO，从而增加邻近透明细胞的质子分泌。因此，RANTES可能参与基底细胞，巨噬细胞和透明细胞之间的串扰，以精细控制最佳酸性腔内环境，这对男性生育能力至关重要。
A complex interplay between different cell types in the epithelium leads to activation of the luminal acidifying capacity of the epididymis, a process that is crucial for sperm maturation and storage. Basal cells sense the luminal angiotensin II (ANG II) and stimulate proton secretion in clear cells through nitric oxide (NO). Our previous study has shown the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) was expressed in the F4/80 positive macrophages of human epididymis. The objective of this study was to explore the involvement of RANTES in regulating the luminal acidification in the rat epididymis. The role of RANTES was investigated by in vivo perfusion with recombinant RANTES, Met-RANTES, and PBS of different pH values. Furthermore, rats vasectomy was performed to alter the epididymal luminal pH. RIA was used to measure the tissue homogenate ANG II concentration. Real time-PCR and western blot were employed to examine the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS in epididymis. RANTES was restricted to the basal macrophages of epididymal ducts and co-localized with its receptors CCR1 and CCR5. Both V-ATPase and iNOS were up-regulated in the cauda epididymis after perfused with recombinant RANTES, while the antagonist Met-RANTES perfusion led to a complete abrogation of the increased expression of V-ATPase in the apical membrane of clear cells and iNOS in macrophages. Upon alkaline perfusion, RANTES expression was significantly increased and the apical accumulation of V-ATPase in the clear cells was induced in the cauda epididymis. The luminal pH in the cauda epididymis increased after vasectomy. The concentration of the ANG II and the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS dropped in the cauda epididymis following vasectomy. Upon the activation of basal cells, RANTES might induce the NO release from macrophages by interacting with its receptors, which increases proton secretion by adjacent clear cells. Thus, RANTES is possible to participate in the crosstalk among basal cells, macrophages and clear cells for the fine control of an optimum acidic luminal environment that is critical for male fertility.