Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-7-22
pubmed:abstractText
L-Arginine plays a central role in the normal function of several organs including the immune system. It is metabolized in macrophages by inducible nitric oxide synthase to produce nitric oxide, important in the cytotoxic mechanisms, and by arginase I (ASE I) and arginase II (ASE II) to synthesize L-ornithine and urea, the first being the precursor for the production of polyamines needed for cell proliferation. L-Arginine availability can modulate T cell function. Human T cells stimulated and cultured in the absence of L-arginine lose the expression of the TCR zeta-chain (CD3zeta) and have an impaired proliferation and a decreased cytokine production. The aim of this work was to test whether activated macrophages could modulate extracellular levels of L-arginine and alter T cell function, and to determine which metabolic pathway was responsible for this event. The results show that macrophages stimulated with IL-4 + IL-13 up-regulate ASE I and cationic amino acid transporter 2B, causing a rapid reduction of extracellular levels of L-arginine and inducing decreased expression of CD3zeta and diminished proliferation in normal T lymphocytes. Competitive inhibitors of ASE I or the addition of excess L-arginine lead to the re-expression of CD3zeta and recovery of T cell proliferation. In contrast, inducible nitric oxide synthase or ASE II failed to significantly reduce the extracellular levels of L-arginine and modulate CD3zeta expression. These results may provide new insights into the mechanisms leading to T cell dysfunction and the down-regulation of CD3zeta in cancer and chronic infectious diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1232-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12874210-Animals, pubmed-meshheading:12874210-Antigens, CD3, pubmed-meshheading:12874210-Arginase, pubmed-meshheading:12874210-Arginine, pubmed-meshheading:12874210-Cationic Amino Acid Transporter 2, pubmed-meshheading:12874210-Cell Division, pubmed-meshheading:12874210-Cells, Cultured, pubmed-meshheading:12874210-Coculture Techniques, pubmed-meshheading:12874210-Down-Regulation, pubmed-meshheading:12874210-Extracellular Space, pubmed-meshheading:12874210-Female, pubmed-meshheading:12874210-Humans, pubmed-meshheading:12874210-Interleukin-13, pubmed-meshheading:12874210-Interleukin-4, pubmed-meshheading:12874210-Jurkat Cells, pubmed-meshheading:12874210-Macrophage Activation, pubmed-meshheading:12874210-Macrophages, Peritoneal, pubmed-meshheading:12874210-Mice, pubmed-meshheading:12874210-Mice, Inbred C57BL, pubmed-meshheading:12874210-T-Lymphocytes, pubmed-meshheading:12874210-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes.
pubmed:affiliation
Tumor Immunology Program, Stanley S Scott Cancer Center, Louisiana State University, Health Sciences Center, New Orleans, LA 70112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.