Regulation of immune responses by L-arginine metabolism

Abstract

L-Arginine is an essential amino acid for birds and young mammals, and it is a conditionally essential amino acid for adult mammals, as it is important in situations in which requirements exceed production, such as pregnancy. Recent findings indicate that increased metabolism of L-arginine by myeloid cells can result in the impairment of lymphocyte responses to antigen during immune responses and tumour growth. Two enzymes that compete for L-arginine as a substrate - arginase and nitric-oxide synthase - are crucial components of this lymphocyte-suppression pathway, and the metabolic products of these enzymes are important moderators of T-cell function. This Review article focuses on the relevance of L-arginine metabolism by myeloid cells for immunity under physiological and pathological conditions.

Arginase blockade protects against hepatic damage in warm ischemia-reperfusion

“…Inhibiting arginase degradation of arginine may lead to decreased downstream products such as polyamines and proline [30]. These products are important mediators of cellular proliferation and collagen synthesis, respectively [31]. Thus, there may be potential adverse effects on liver regeneration and wound healing in animals treated with an arginase inhibitor.…”

Susceptibility to Yersinia pseudotuberculosis Infection is Linked to the Pattern of Macrophage Activation

“…The activation by the classical pathway results in the production of NO, synthesized from arginine by inducible NO synthase (iNOS) [13,17]. The alternative metabolic pathway for arginine is catalysed by arginase, which converts arginine to ornithine and urea [13].…”

“…The activation by the classical pathway results in the production of NO, synthesized from arginine by inducible NO synthase (iNOS) [13,17]. The alternative metabolic pathway for arginine is catalysed by arginase, which converts arginine to ornithine and urea [13]. It has been shown that macrophages from Th1 strains of mice (C57BL ⁄ 6, B10D2) preferentially use the iNOS pathway and macrophages from Th2 strains of mice (BALB ⁄ c, DBA ⁄ 2) preferentially use the arginase pathway [15].…”

“…Microbial antigens, tumour products, effector T cells and their secretory products influence the heterogeneity and the state of activation of macrophage populations [12,13].…”

Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction

“…22 In the B6SJLF1 model, where myeloid cell expansion is more protracted, an extrinsic regulatory role of these cells on the observed in vitro T-cell proliferative responses cannot be excluded. The expansion of myeloid progenitor cells in these chimeras is reminiscent of the myeloid-derived suppressor cells described in association with myelosuppression, GvHD, tumors and chronic infections 21,29 where they have been implicated in tumor-specific and nonspecific T-cell dysfunction. [30][31][32] Our earlier data, 21 and more recently those of others, 33 suggest that these cells may have a role in controlling GvH reactivity.…”