Cocchiara R, Albeggiani G, Azzolina A, Bongiovanni A, Lampiasi N, Di Blasi F, Geraci D
Instituto di Biologia dello Sviluppo, CNR, Palermo, Italy.
J Neuroimmunol. 1995 Jul;60(1-2):107-15. doi: 10.1016/0165-5728(95)00060-f.
There is increasing evidence that neuropeptides, steroid hormones and inflammatory cytokines influence the immune response during the reproductive cycle. In the present study, we focus on the effects of neuropeptide Substance P (SP) during the pre-implantation stage of embryo development (day 4 of pregnancy), at pro-estrus and di-estrus (two phases with different hormonal states). We found heterogeneous responses to SP and anti-IgE by the rat uterine mast cells (MCs), as detected by ELISA. In fact, MCs purified from uteri on day 4 of pregnancy released histamine, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in response to anti-IgE, but not to SP. When pre-incubated with SP, the release to anti-IgE was significantly enhanced compared to anti-IgE alone. Exposure of SP to antibodies to SP, prior to pre-incubation with MCs, negated the SP effect on IgE-mediated release. At the pro-estrus phase SP showed similar behavior as on day 4 of pregnancy, whereas at the di-estrus phase SP alone was capable of inducing release of histamine and cytokines from purified uterine MCs. Moreover, non-quantitative RT-PCR analysis of the TNF-alpha mRNA level suggested an SP stimulation at the di-estrus phase, but neither on day 4 of pregnancy nor at the pro-estrus phase. Taken together, these data strongly suggest that SP can modulate IgE-mediated uterine MC release of histamine and inflammatory cytokines in different ways, depending on the phase of the reproductive cycle.
越来越多的证据表明，神经肽、类固醇激素和炎性细胞因子在生殖周期中影响免疫反应。在本研究中，我们聚焦于神经肽P物质（SP）在胚胎发育植入前阶段（妊娠第4天）、动情前期和动情后期（两种具有不同激素状态的阶段）的作用。通过酶联免疫吸附测定法（ELISA）检测发现，大鼠子宫肥大细胞（MCs）对SP和抗IgE有不同的反应。事实上，从妊娠第4天子宫中纯化的MCs对抗IgE有反应，可释放组胺、粒细胞巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子-α（TNF-α），但对SP无反应。当与SP预孵育时，与单独使用抗IgE相比，对抗IgE的释放显著增强。在与MCs预孵育之前，将SP与抗SP抗体接触，可消除SP对IgE介导释放的作用。在动情前期，SP表现出与妊娠第4天相似的行为，而在动情后期，单独的SP能够诱导纯化的子宫MCs释放组胺和细胞因子。此外，TNF-α mRNA水平的非定量逆转录聚合酶链反应（RT-PCR）分析表明，在动情后期有SP刺激，但在妊娠第4天和动情前期均无。综上所述，这些数据强烈表明，SP可根据生殖周期的阶段，以不同方式调节IgE介导的子宫MCs组胺和炎性细胞因子的释放。
