L-Arginine modulates neonatal lymphocyte proliferation through an interleukin-2 independent pathway.
In cases of arginine depletion, lymphocyte proliferation, cytokine production and CD3ζ chain expression are all diminished. In addition to myeloid suppressor cells, polymorphonuclear cells (PMN) also exert T-cell immune suppressive effects through arginase-induced l-arginine depletion, especially during pregnancy. In this study, we investigated how arginase/l-arginine modulates neonatal lymphocyte proliferation. Results showed that the neonatal plasma l-arginine level was lower than in adults (48·1 ± 11·3 versus 86·5 ± 14·6 μm; P = 0·003). Neonatal PMN had a greater abundance of arginase I protein than adult PMN. Both transcriptional regulation and post-transcriptional regulation were responsible for the higher arginase I expression of neonatal PMN. Exogenous l-arginine enhanced neonate lymphocyte proliferation but not that of adult cells. The RNA-binding protein HuR was important but was not the only modulation factor in l-arginine-regulated neonatal T-cell proliferation. l-Arginine-mediated neonatal lymphocyte proliferation could not be blocked by interleukin-2 receptor blocking antibodies. These results suggest that the altered arginase/l-arginine cascade may be one of the mechanisms that contribute to altered neonatal immune responses. Exogenous l-arginine could enhance neonate lymphocyte proliferation through an interleukin-2-independent pathway.
Department of Paediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Centre, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiug, Taiwan.
Hong-Ren
HR
Yu
Ho-Chang
HC
Kuo
Li-Tung
LT
Huang
Chih-Cheng
CC
Chen
You-Lin
YL
Tain
Jiunn-Ming
JM
Sheen
Mao-Meng
MM
Tiao
Hsin-Chun
HC
Huang
Kuender D
KD
Yang
Chia-Yo
CY
Ou
Te-Yao
TY
Hsu
D000328:Adult; D000367:Age Factors; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
D051959:ELAV Proteins; C508594:IL2 protein, human; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D001120:Arginine; C574619:ARG1 protein, human; D001119:Arginase
arginase; interleukin-2; l-arginine; lymphocyte proliferation; neonate