Wan Hui, Versnel Marjan A, Cheung Wai Yee, Leenen Pieter J M, Khan Nisar A, Benner Robbert, Kiekens Rebecca C M
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
J Leukoc Biol. 2007 Oct;82(4):926-33. doi: 10.1189/jlb.0207092. Epub 2007 Jul 11.
Human chorionic gonadotropin (hCG) is a placental glycoprotein, mainly secreted by trophoblasts during pregnancy. Its function in endocrine regulation has been well documented, but its immunological role is still largely unclear. For a successful pregnancy, an effective innate immunity is needed to protect the mother and fetus against infection, while maintaining tolerance against the paternal antigens of the fetus. The aim of this study was to investigate the effect of hCG on the function of macrophages (Mvarphi), which are major players in the innate response. hCG treatment of IFN-gamma-primed Mvarphi resulted in increased production of NO, reactive oxygen species, IL-6 and IL-12p40, and enhanced phagocytosis of apoptotic cells. hCG treatment did not affect the induction of allogeneic T cell proliferation by IFN-gamma-primed Mvarphi. The observed effects were receptor-mediated and involved the protein kinase A signaling pathway, as indicated by blocking studies using specific inhibitors. In vivo thioglycollate-elicited Mvarphi also exhibited increased phagocytic ability upon IFN-gamma activation and hCG treatment. In conclusion, hCG enhances Mvarphi functions involved in innate immunity, while the capacity to stimulate allogeneic T cells remains unchanged.
人绒毛膜促性腺激素(hCG)是一种胎盘糖蛋白,主要由孕期的滋养层细胞分泌。其在内分泌调节中的功能已有充分记载,但其免疫作用仍大多不明。为实现成功妊娠,需要有效的先天免疫来保护母体和胎儿免受感染,同时维持对胎儿父源抗原的耐受。本研究的目的是调查hCG对巨噬细胞(Mφ)功能的影响,巨噬细胞是先天免疫反应的主要参与者。用hCG处理经γ干扰素预处理的Mφ,可导致一氧化氮、活性氧、白细胞介素-6和白细胞介素-12p40的产生增加,并增强对凋亡细胞的吞噬作用。hCG处理不影响经γ干扰素预处理的Mφ诱导异体T细胞增殖。如使用特异性抑制剂进行的阻断研究所表明,观察到的效应是受体介导的,且涉及蛋白激酶A信号通路。体内经巯基乙酸诱导的Mφ在γ干扰素激活和hCG处理后也表现出吞噬能力增强。总之,hCG增强了参与先天免疫的Mφ功能,而刺激异体T细胞的能力保持不变。