Fitterer Raphaela, Lajqi Trim, Kranig Simon Alexander, Braun Maylis, Theissig Nicole, Kuss Navina, Pöschl Johannes, Frommhold David, Hudalla Hannes
Department of Neonatology, Heidelberg University Children's Hospital, 69120 Heidelberg, Germany.
Klinik für Kinderheilkunde und Jugendmedizin, 87700 Memmingen, Germany.
J Clin Med. 2020 Aug 27;9(9):2772. doi: 10.3390/jcm9092772.
(1) Background: L-arginine is a complex modulator of immune functions, and its levels are known to decrease under septic conditions. L-arginine may suppress leukocyte recruitment in vivo; however, little is known about the gestational age-specific effects of L-arginine on leukocyte recruitment in preterm infants. We now asked whether L-arginine alters leukocyte recruitment in preterm and term neonates. (2) Methods: Leukocytes were isolated from preterm (28 + 0 to 32 + 6 weeks of gestation) and term (>37 weeks of gestation) newborns as well as from healthy adults. After incubation with 10 µg/mL L-arginine, we assessed leukocyte rolling and adhesion in dynamic microflow chamber experiments and leukocyte transmigration in fluorescence assays. In addition, we measured the expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg-1) in neutrophils by flow cytometry. (3) Results: Leukocyte rolling, adhesion, and transmigration increased with gestational age. Leukocyte rolling, adhesion, and transmigration were decreased by L-arginine in term-born infants and adults. Preterm leukocytes showed no change in recruitment upon L-arginine exposure. Leukocyte adhesion after L-arginine exposure reached similar levels among all groups. In line, the expression of iNOS and Arg-1 was similar in all three age groups. (4) Conclusion: L-arginine dampens the ex vivo recruitment capacity of leukocytes from term-born infants, whereas no effect was seen in premature infants. As levels of iNOS and Arg-1 in neutrophils remain ontogenetically unchanged, the anti-inflammatory effect of L-arginine on the leukocyte recruitment cascade needs further investigation. These results add to the controversial debate of L-arginine supplementation in premature infants in sepsis.
(1) 背景：L-精氨酸是免疫功能的复杂调节剂，已知其水平在脓毒症情况下会降低。L-精氨酸可能在体内抑制白细胞募集；然而，关于L-精氨酸对早产儿白细胞募集的胎龄特异性影响知之甚少。我们现在探究L-精氨酸是否会改变早产儿和足月儿的白细胞募集。(2) 方法：从早产（妊娠28 + 0至32 + 6周）和足月（>37周妊娠）新生儿以及健康成年人中分离白细胞。在与10 µg/mL L-精氨酸孵育后，我们在动态微流腔实验中评估白细胞滚动和黏附，并在荧光测定中评估白细胞迁移。此外，我们通过流式细胞术测量中性粒细胞中诱导型一氧化氮合酶（iNOS）和精氨酸酶1（Arg-1）的表达。(3) 结果：白细胞滚动、黏附和迁移随胎龄增加。L-精氨酸使足月儿和成年人的白细胞滚动、黏附和迁移减少。早产白细胞在暴露于L-精氨酸后募集无变化。L-精氨酸暴露后的白细胞黏附在所有组中达到相似水平。同样，所有三个年龄组中iNOS和Arg-1的表达相似。(4) 结论：L-精氨酸减弱了足月儿白细胞的体外募集能力，而未观察到对早产儿有影响。由于中性粒细胞中iNOS和Arg-1的水平在个体发育上保持不变，L-精氨酸对白细胞募集级联反应的抗炎作用需要进一步研究。这些结果增加了关于败血症早产儿补充L-精氨酸的争议性辩论。
