L-Arginine Modulates Neonatal Leukocyte Recruitment in a Gestational Age-Dependent Manner

• Published in: Journal of clinical medicine 2020-08, Vol.9 (9), p.2772
• Main Authors: Fitterer, Raphaela, Lajqi, Trim, Kranig, Simon Alexander, Braun, Maylis, Theissig, Nicole, Kuss, Navina, Pöschl, Johannes, Frommhold, David, Hudalla, Hannes
• Format: Article
• Language: English
• Subjects: Blood; Blood vessels; Chemokines; Clinical medicine; Ethics; Experiments; Flow cytometry; Gestational age; Granulocytes; Immune system; Laboratories; Neutrophils; Newborn babies; Premature babies; Premature birth; Recruitment; Sepsis; Shear stress; Software; Viscosity
• ISSN: 2077-0383; 2077-0383
• 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.