Buschmann Kirsten, Tschada Raphaela, Metzger Marie-Sophie, Braach Natascha, Kuss Navina, Hudalla Hannes, Poeschl Johannes, Frommhold David
Department of Neonatology, University Hospital, 69120, Heidelberg, Germany.
BMC Immunol. 2014 Nov 27;15:53. doi: 10.1186/s12865-014-0053-0.
Insufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants. Since the receptor of advanced glycation end products (RAGE) is a known leukocyte adhesion molecule and highly expressed during early development, we asked whether RAGE plays a role for leukocyte recruitment in preterm and term infants.
Leukocyte adhesion was analyzed in dynamic flow chamber experiments using isolated leukocytes of cord blood from extremely premature (<30 weeks of gestation), moderately premature (30-35 weeks of gestation) and mature neonates (>35 weeks of gestation) and compared to the results of adults. For fluorescent microscopy leukocytes were labeled with rhodamine 6G. In the respective age groups we also measured the plasma concentration of soluble RAGE (sRAGE) by ELISA and Mac-1 and LFA-1 expression on neutrophils by flow cytometry.
The adhesive functions of fetal leukocytes significantly increase with gestational age. In all age groups, leukocyte adhesion was crucially dependent on RAGE. In particular, RAGE was equally effective to mediate leukocyte adhesion when compared to ICAM-1. The plasma levels of sRAGE were high in extremely premature infants and decreased with increasing gestational age. In contrast, expression of β2-Integrins Mac-1 and LFA-1 which are known ligands for RAGE and ICAM-1 did not change during fetal development.
We conclude that RAGE is a crucial leukocyte adhesion molecule in both preterm and term infants.
白细胞募集不足可能是早产儿发生危及生命感染的高发病率的原因之一。由于晚期糖基化终产物受体（RAGE）是一种已知的白细胞粘附分子，且在早期发育过程中高度表达，我们探讨RAGE在早产儿和足月儿的白细胞募集中是否发挥作用。
使用来自极早产儿（<30周妊娠）、中度早产儿（30 - 35周妊娠）和成熟新生儿（>35周妊娠）的脐血分离的白细胞，在动态流动腔实验中分析白细胞粘附，并与成人结果进行比较。对于荧光显微镜检查，白细胞用罗丹明6G标记。在各个年龄组中，我们还通过ELISA测量可溶性RAGE（sRAGE）的血浆浓度，并通过流式细胞术测量中性粒细胞上Mac-1和LFA-1的表达。
胎儿白细胞的粘附功能随胎龄显著增加。在所有年龄组中，白细胞粘附关键依赖于RAGE。特别是，与ICAM-1相比，RAGE在介导白细胞粘附上同样有效。极早产儿的sRAGE血浆水平较高，并随胎龄增加而降低。相比之下，已知为RAGE和ICAM-1配体的β2整合素Mac-1和LFA-1的表达在胎儿发育过程中没有变化。
我们得出结论，RAGE在早产儿和足月儿中都是关键的白细胞粘附分子。
