The Metabolism of L-Arginine and Its Importance in Immune Function
DOI:
https://doi.org/10.15173/m.v1i26.947Abstract
The importance of arginine in maintaining the homeostasis of the
immune system is a focus of the emerging field of immunometabolism,
and is representative of the growing body of knowledge on the role of
metabolites in immune function. Arginine plays a critical role in the function
of the immune system, as arginine deficiency in macrophages leads to a
defect in nitric oxide production. Consequently, this results in decreased
macrophage elimination of pathogens. Additionally, myeloid suppressor
cells (MSCs) have been shown to exert regulatory effects on activated
T-cells by utilizing arginine metabolism in various different pathways.
Decreased levels of arginine have also been observed to interfere with
proper B-cell maturation and IgM production, all of which ultimately impair
the adaptive immune response. In this review, the importance of arginine
in the context of immune system is explored.
References
Mathis D, Shoelson SE. Immunometabolism:
an emerging frontier. Nat Rev Immunol.
Feb;11(2):81-83
Ferrante AW. Macrophages, fat, and the
emergence of immunometabolism. J Clin
Invest. 2013 Dec 2;123(12):4992–3.
Saric J. Interactions between immunity
and metabolism - contributions
from the metabolic profiling of parasiterodent
models. Parasitology. 2010
Aug;137(9):1451–66.
Popovic PJ, Zeh HJ, Ochoa JB. Arginine
and immunity. J Nutr. 2007 Jun;137(6
Suppl 2):1681S – 1686S.
Wu G, Morris SM. Arginine metabolism:
nitric oxide and beyond. Biochem J.
Nov;336 ( Pt 1):1–17.
Mortimore GE, Pösö AR. Intracellular
protein catabolism and its control during
nutrient deprivation and supply. Annu Rev
Nutr. 1987;7:539–64.
Nagamani SCS, Erez A, Lee B. Argininosuccinate
lyase deficiency. Genetics in
Medicine. 2012 May;14(5):501–7.
Murphy K. Janeway’s immunobiology.
th ed. New York: Garland Science;
868 p.
MacMicking J, Xie QW, Nathan C. Nitric
oxide and macrophage function. Annu
Rev Immunol. 1997;15:323–50.
Tayeh MA, Marletta MA. Macrophage oxidation
of L-arginine to nitric oxide, nitrite,
and nitrate. Tetrahydrobiopterin is required
as a cofactor. J Biol Chem. 1989
Nov 25;264(33):19654–8.
Croen KD. Evidence for antiviral effect of
nitric oxide. Inhibition of herpes simplex
virus type 1 replication. J Clin Invest.
Jun;91(6):2446–52.
Benencia, Courreges. Nitric oxide and
macrophage antiviral extrinsic activity.
Immunology. 1999 Nov;98(3):363–70.
Bronte V, Serafini P, Mazzoni A, Segal
DM, Zanovello P. L-arginine metabolism
in myeloid cells controls T-lymphocyte
functions. Trends Immunol. 2003
Jun;24(6):302–6.
Sears R, Nuckolls F, Haura E, Taya Y, Tamai
K, Nevins JR. Multiple Ras-dependent
phosphorylation pathways regulate Myc
protein stability. Genes Dev. 2000 Oct
;14(19):2501–14.
Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-
Carnero C, Hukelmann JL, Rolf J, et
al. PDK1 regulation of mTOR and hypoxia-
inducible factor 1 integrate metabolism
and migration of CD8+ T cells. J Exp
Med. 2012 Dec 17;209(13):2441–53.
Powell JD, Delgoffe GM. The mammalian
target of rapamycin: linking T cell differentiation,
function, and metabolism. Immunity.
Sep 24;33(3):301–11.
Brito C, Naviliat M, Tiscornia AC, Vuillier F,
Gualco G, Dighiero G, et al. Peroxynitrite
inhibits T lymphocyte activation and proliferation
by promoting impairment of tyrosine
phosphorylation and peroxynitritedriven
apoptotic death. J Immunol. 1999
Mar 15;162(6):3356–66.
Bronte V, Kasic T, Gri G, Gallana K, Borsellino
G, Marigo I, et al. Boosting antitumor
responses of T lymphocytes infiltrating
human prostate cancers. J Exp Med.
Apr 18;201(8):1257–68.
Sugimura K, Wada Y, Kimura T, Ohno
T, Kobayashi S, Azuma I. Inherited hyperactivation
of L-arginine synthesis in
gamma + B lymphocytes of systemic
autoimmune MRL mice. Int Immunol.
;2(11):1033–8.
Mannick JB, Asano K, Izumi K, Kieff E,
Stamler JS. Nitric oxide produced by human
B lymphocytes inhibits apoptosis
and Epstein-Barr virus reactivation. Cell.
Dec;79(7):1137–46.
De Jonge WJ, Kwikkers KL, te Velde AA,
van Deventer SJH, Nolte MA, Mebius RE,
et al. Arginine deficiency affects early
B cell maturation and lymphoid organ
development in transgenic mice. J Clin
Invest. 2002 Nov;110(10):1539–48.
Hobbs JR. IgM deficiency. Birth Defects
Orig Artic Ser. 1975;11(1):112–6.
Kudsk KA, Minard G, Croce MA, Brown
RO, Lowrey TS, Pritchard FE, et al. A randomized
trial of isonitrogenous enteral
diets after severe trauma. An immuneenhancing
diet reduces septic complications.
Ann Surg. 1996 Oct;224(4):531–
; discussion 540–3.
