Giaglis Stavros, Stoikou Maria, Sur Chowdhury Chanchal, Schaefer Guenther, Grimolizzi Franco, Rossi Simona W, Hoesli Irene Mathilde, Lapaire Olav, Hasler Paul, Hahn Sinuhe
Department of Biomedicine, University Hospital Basel, Basel, Switzerland; Department of Rheumatology, Cantonal Hospital Aarau, Aarau, Switzerland.
Department of Biomedicine, University Hospital Basel , Basel , Switzerland.
Front Immunol. 2016 Dec 5;7:565. doi: 10.3389/fimmu.2016.00565. eCollection 2016.
Human pregnancy is associated with a mild pro-inflammatory state, characterized by circulatory neutrophil activation. In order to explore the mechanism underlying this alteration, we examined NETosis during normal gestation. Our data indicate that neutrophils exhibit a pro-NETotic state, modulated in a multimodal manner during pregnancy. In general, circulatory granulocyte colony-stimulating factor, the levels of which increase during gestation, promotes neutrophil extracellular trap (NET) formation. Early in pregnancy, NETosis is enhanced by chorionic gonadotropin, whereas toward term is stimulated by estrogen. A complex interaction between estrogen and progesterone arises, wherein progesterone restrains the NETotic process. In this state, extensive histone citrullination is evident, yet full NETosis is inhibited. This coincides with the inability of neutrophil elastase to translocate from the cytoplasm to the nucleus and is regulated by progesterone. Our findings provide new insight concerning gestational and hormone-driven pathologies, since neutrophil recruitment, activation, and NET release could be associated with excessive endothelial and placental injury.
人类妊娠与轻度促炎状态相关，其特征为循环中性粒细胞活化。为了探究这种改变背后的机制，我们研究了正常妊娠期间的中性粒细胞胞外诱捕网形成（NETosis）。我们的数据表明，中性粒细胞呈现出促NETosis状态，在妊娠期间以多模式方式受到调节。一般来说，循环中的粒细胞集落刺激因子在妊娠期间水平升高，它会促进中性粒细胞胞外诱捕网（NET）的形成。妊娠早期，绒毛膜促性腺激素会增强NETosis，而在足月时则由雌激素刺激。雌激素和孕酮之间会产生复杂的相互作用，其中孕酮会抑制NETosis过程。在这种状态下，广泛的组蛋白瓜氨酸化很明显，但完整的NETosis受到抑制。这与中性粒细胞弹性蛋白酶无法从细胞质转运到细胞核相吻合，并且受孕酮调节。我们的研究结果为妊娠和激素驱动的病理状况提供了新的见解，因为中性粒细胞的募集、活化和NET释放可能与过度的内皮和胎盘损伤有关。
