Nitrogen Oxide Levels in Patients After Trauma and During Sepsis

Ochoa, Juan B.; Udekwu, Anthony O.; Billiar, Timothy R.; Curran, Ronald; Cerra, Frank B.; Simmons, Richard L.; Peitzman, Andrew B.

doi:10.1097/00000658-199111000-00013

Cited by 573 publications

(229 citation statements)

References 31 publications

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“…L-Arginine is also metabolized in macrophages by iNOS to citrulline and nitric oxide, a highly reactive compound important in the cytotoxic mechanism of these cells (4,5). The importance of L-arginine on the immune response was suggested by the marked association of impaired T cell function in patients and rodents after liver transplantation or trauma (11,12,26,27), which rapidly recovered with the enteral or parenteral supplementation of L-arginine (14 -16, 28). L-Arginine levels in serum range from 50 to 150 M. The mechanism by which L-arginine depletion causes T cell dysfunction is incompletely understood.…”

Section: Discussionmentioning

confidence: 99%

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Rodríguez

Zea

DeSalvo

et al. 2003

The Journal of Immunology

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416

346

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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 ζ-chain (CD3ζ) 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 CD3ζ 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 CD3ζ 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 CD3ζ expression. These results may provide new insights into the mechanisms leading to T cell dysfunction and the down-regulation of CD3ζ in cancer and chronic infectious diseases.

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Section: Discussionmentioning

confidence: 99%

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Rodríguez

Zea

DeSalvo

et al. 2003

The Journal of Immunology

Self Cite

416

346

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show abstract

“…[24] Evidence for up-regulation of iNOS in humans under conditions similar to the animal models came first from a study in septic patients, demonstrating a four-fold increase in circulating levels of reactive nitrogen species. [26] Similarly, iNOS mRNA is present in human liver following trauma. [19] Thus, ample evidence exists that iNOS expression is part of the pathophysiology of sepsis and shock.…”

Section: Nitric Oxide Synthesis and The Livermentioning

confidence: 99%

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz¹,

Kim²,

Bagci³

et al. 2004

CMM

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“…The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population 9 Therefore, altered NO levels have been reported to be related to many conditions and activities such as sepsis, 26 reproduction, 33 infection, 8 hypertension, 20 exercise, 21 diabetes, 44 hypoxia, 23 and cancer. 37 In particular, reduced NO levels can result in cardiovascular disease, carotid atherosclerosis, hypertension, and aortic aneurysm.…”

mentioning

confidence: 99%

The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population

Kim

Baek

et al. 2011

FOC

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Object Some genetic factors are known to be associated with the formation of cerebral aneurysms in the Caucasian population. One of these factors is endothelial nitric oxide synthase (eNOS) gene polymorphisms. Endothelial nitric oxide synthase genes encode eNOS, which synthesizes NO from l-arginine. There continues to be controversy about the relationships between eNOS gene polymorphisms and the formation of intracranial aneurysms. In this study, the authors evaluated these relationships in the Korean population. Methods Three eNOS polymorphisms (eNOS 27VNTR, T786C, and G894T) were genotyped in 96 patients with ruptured aneurysms, 53 patients with unruptured aneurysms, and in 121 volunteers via polymerase chain reaction–restriction fragment length polymorphism analysis. Results The mean ages of the patients and healthy volunteers were 52.9 ± 12.3 years and 55.2 ± 9.1 years, respectively. The patient group was composed of 56 men and 93 women, and the healthy volunteer group was composed of 46 men and 75 women. Only the incidence of smoking history was significantly higher in the patient group than in the control group (p = 0.001). The genotypic frequencies for the 3 eNOS gene polymorphisms were in agreement with those predicted by Hardy-Weinberg equilibrium. There were no significant associations between the eNOS recessive models and the formation of an aneurysm. The authors found no genotypic differences between similar races among patients with aneurysms. Conclusions The present study shows that eNOS 27VNTR, T786C, and G894T polymorphisms cannot be used as indicators of the formation of intracranial aneurysms in Korean patients. To confirm these findings an additional analyses might need to be performed using a larger sample size. There were no differences in the genotypic distributions and allelic frequencies between similar races among patients with aneurysms, which were the same in previously reported normal populations.

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Nitrogen Oxide Levels in Patients After Trauma and During Sepsis

Cited by 573 publications

References 31 publications

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population

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