Rakova Natalia, Muller Dominik N, Staff Anne Cathrine, Luft Friedrich C, Dechend Ralf
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
Department of Obstetrics and Gynaecology, Oslo University Hospital, Ulleval, Norway; Faculty of Medicine, University of Oslo, Norway.
J Reprod Immunol. 2014 Mar;101-102:135-139. doi: 10.1016/j.jri.2013.04.001. Epub 2013 May 30.
The molecular mechanisms leading to preeclampsia are poorly understood. It has been related to certain immune mechanisms, as well as the pathological regulation of the renin-angiotensin system together with perturbed salt and plasma volume regulation. Finally, a non-specific, vascular, inflammatory response is generated, which leads to the clinical syndrome. Here, we present novel findings in salt (NaCl) metabolism implying that salt is not only important in blood pressure control and volume homeostasis, but also in immune regulation. Sodium and chloride can be stored without accumulation of water in the interstitium at hypertonic concentrations through interactions with proteoglycans. Macrophages in the interstitium act as osmosensors for salt, producing increased amounts of vascular endothelial factor C, which increases the density of the lymph-capillary network and the production of nitric oxide in vessels. An increased interstitial salt concentration activates the innate immune system, especially Th17 cells, and may be an important trigger for autoimmune diseases. The novel findings with the idea of sodium storage and local mechanisms of volume and immune regulation are appealing for preeclampsia and may unify the "immune" and "vascular" hypotheses of preeclampsia.
导致先兆子痫的分子机制尚不清楚。它与某些免疫机制有关，也与肾素 - 血管紧张素系统的病理调节以及盐和血容量调节紊乱有关。最后，会产生一种非特异性的血管炎症反应，从而导致临床综合征。在此，我们展示了盐（氯化钠）代谢方面的新发现，这表明盐不仅在血压控制和容量稳态中很重要，而且在免疫调节中也很重要。通过与蛋白聚糖相互作用，钠和氯可以在高渗浓度下存储于间质中而不伴有水的蓄积。间质中的巨噬细胞作为盐的渗透压感受器，会产生更多的血管内皮生长因子C，这会增加淋巴毛细血管网络的密度以及血管中一氧化氮的生成。间质盐浓度升高会激活先天免疫系统，尤其是Th17细胞，并且可能是自身免疫性疾病的一个重要触发因素。关于钠存储以及容量和免疫调节局部机制的新发现对先兆子痫具有吸引力，并且可能统一先兆子痫的“免疫”和“血管”假说。
