Cat2 l-arginine transporter-deficient fibroblasts can sustain nitric oxide production

Nicholson, Benjamin; Manner, Cathyryne K.; MacLeod, Carol L.

doi:10.1016/s1089-8603(02)00116-7

Cited by 25 publications

(19 citation statements)

References 44 publications

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“…However, the background of KO animals (C57BL/6 or BALB/c) does not explain these discrepancies because similar results were found when we used the two strains (data not shown). It should be noted that for these authors, the production of NO in fibroblasts and astrocytes is not completely dependent on CAT2 (35,36).…”

Section: Discussionmentioning

confidence: 79%

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Yeramian

Martín

Serrat

et al. 2006

The Journal of Immunology

121

110

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Arginine is processed by macrophages in response to the cytokines to which these cells are exposed. Th1-type cytokines induce NO synthase 2, which metabolizes arginine into nitrites, while the Th2-type cytokines produce arginase, which converts arginine into polyamines and proline. Activation of bone marrow-derived macrophages by these two types of cytokines increases l-arginine transport only through the y+ system. Analysis of the expression of the genes involved in this system showed that Slc7A1, encoding cationic amino acid transporters (CAT)1, is constitutively expressed and is not modified by activating agents, while Slc7A2, encoding CAT2, is induced during both classical and alternative activation. Macrophages from Slc7A2 knockout mice showed a decrease in l-arginine transport in response to the two kinds of cytokines. However, while NO synthase 2 and arginase expression were unmodified in these cells, the catabolism of arginine was impaired by both pathways, producing smaller amounts of nitrites and also of polyamines and proline. In addition, the induction of Slc7A2 expression was independent of the arginine available and of the enzymes that metabolize it. In conclusion, the increased arginine transport mediated by activators is strongly regulated by CAT2 expression, which could limit the function of macrophages.

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Section: Discussionmentioning

confidence: 79%

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Yeramian

Martín

Serrat

et al. 2006

The Journal of Immunology

121

110

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show abstract

“…For example, mice that are homozygous null for Slc7a2 show a reduction in nitric oxide production in macrophages and fibroblasts, important in immune response and wound healing. 30,31 Mice homozygous null for Mgat2 show early post-natal lethality and a number of other defects. 32 Decreases in Tnnt1 and increases in Synj1 have been found to be markers for stem cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Creation and implications of a phenome-genome network

2006

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“…However, other cell types (i.e., fibroblasts) are able to produce NO even in the absence of CAT2 (12). Because alveolar macrophages differ from monocytes and macrophages from other locations in many aspects (18,19) and because NO was suggested as a potential mechanism of action for alveolar macrophage-mediated suppression of lung inflammation (15), we tested the hypothesis that CAT2 was required for NOS activity in alveolar macrophages.…”

Section: Cat2 Is Required For Nos Activity In Alveolar Macrophagesmentioning

confidence: 99%

“…Although these mice are grossly normal, their peritoneal macrophages have a 95% decrease in L-arginine uptake and a marked impairment in NO production (10,11). In contrast, fibroblasts are able to compensate for CAT2-deficiency and have only mild impairment in NO production (12). Because arginine entry into the NOS and arginase pathways could have multiple effects on lung inflammation, both positive and negative, we used CAT2-deficient mice to test the net effect of reducing transport of arginine into macrophages, hypothesizing that transport of arginine via CAT2 has an important role in lung inflammation.…”

mentioning

confidence: 99%

Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung

Rothenberg

Doepker

Lewkowich³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Arginine is an amino acid that serves as a substrate for nitric oxide synthase and arginase. As such, arginine has the potential to influence diverse fundamental processes in the lung. Here we report that the arginine transport protein, cationic amino acid transporter (CAT)2, has a critical role in regulating lung inflammatory responses. Analysis of CAT2-deficient mice revealed spontaneous inflammation in the lung. Marked eosinophilia, associated with up-regulation of eotaxin-1, was present in the bronchoalveolar lavage fluid of 3-week-old CAT2-deficient mice. The eosinophilia was gradually replaced by neutrophilia in adult mice, while eotaxin-1 levels decreased and GRO-␣ levels increased. Despite the presence of activated alveolar macrophages in CAT2-deficient mice, NO production was compromised in these cells. Examination of dendritic cell activation, which can be affected by NO release, indicated increased dendritic cell activation in the lungs of CAT2-deficient mice. This process was accompanied by an increase in the number of memory T cells. Thus, our data suggest that CAT2 regulates anti-inflammatory processes in the lungs via regulation of dendritic cell activation and subsequent T cell responses.inflammation ͉ dendritic cells ͉ arginase ͉ nitric oxide

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Cat2 l-arginine transporter-deficient fibroblasts can sustain nitric oxide production

Cited by 25 publications

References 44 publications

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Creation and implications of a phenome-genome network

Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung

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