Nitric oxide: A cytotoxic activated macrophage effector molecule

Hibbs, John B.; Taintor, Read R.; Vavrin, Zdenek; Rachlin, Elliot M.

doi:10.1016/s0006-291x(88)80015-9

Cited by 1,897 publications

(890 citation statements)

References 25 publications

Supporting

Mentioning

841

Contrasting

Unclassified

Order By: Relevance

“…Hydrogen peroxide was purchased from J.T. Baker (Deventer, Holland); [2,3,4,5] The macrophage cell line, NR8383 was kindly provided by R.J. Helmke, (Dept of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA). Klebsiella Pneumoniae were a kind gift from J. van Amsterdam (Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, the Netherlands).…”

Section: Chemicalsmentioning

confidence: 99%

“…Nitric oxide (NO) is a free radical that is known to have an important function as mediator in several biological processes amongst which, vasorelaxation [1,2], cellmediated immune responses [3,4], inhibition of platelet aggregation [5] and neurotransmission [6] are extensively investigated. The formation of NO has been described in many mammalian cell types and can be ascribed to three isoforms of nitric oxide synthase (NOS), all of which oxidize L-arginine to L-citrulline.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

View full text Add to dashboard Cite

The nasal decongestants oxymetazoline and xylometazoline are frequently used in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, the aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (iNOS) and the constitutive isoform of NO synthase (cNOS).Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3 H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3 H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor.Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3 H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected.As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. Eur Respir J 2000; 16: 437±444.

show abstract

Section: Chemicalsmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…It is clear that the NO generated by activated macrophages contributes to their cytotoxic properties against tumor cells, parasitic fungi, intracellular bacteria, protozoans, and helminths (6,61). Killing of tumor cells and fungi is associated with depletion of intracellular iron from the target cells (61).…”

Section: Nitric Oxide In the Immune Response Inflammation And Tissumentioning

confidence: 99%

Nitric oxide and arthritis

Stefanović-Račić

Stadler

Evans

1993

Arthritis & Rheumatism

273

136

View full text Add to dashboard Cite

“…NO is produced by various iso-enzymes of NOS, and as NOS expression increases, so do other NO related metabolic constitutions such as nitrotryosine. These NO byproducts appear in a variety of human tumors including breast cancer [3,9,10,16,18,19,21], and in tumor-infiltrating macrophages, endothelial cells, and/or tumor cells [22,23]. By example, in a large (n0161) study of breast tumors, 61 % were found to express iNOS, and within that group, iNOS up-regulation was a marker for tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines

et al. 2012

View full text Add to dashboard Cite

There is a lack of understanding of the casual mechanisms behind the observation that some breast adenocarcinomas have identical morphology and comparatively different cellular growth behavior. This is exemplified by a differential response to radiation, chemotherapy, and other biological intervention therapies. Elevated concentrations of the free radical nitric oxide (NO), coupled with the upregulated enzyme nitric oxide synthase (NOS) which produces NO, are activities which impact tumor growth. Previously, we adapted four human breast cancer cell lines: BT-20, Hs578T, T-47D, and MCF-7 to elevated concentrations of nitric oxide (or high NO [HNO]). This was accomplished by exposing the cell lines to increasing levels of an NO donor over time. Significantly, the HNO cell lines grew faster than did each respective ("PARENT") cell line even in the absence of NO donor-supplemented media. This was evident despite each "parent" being morphologically equivalent to the HNO adapted cell line. Herein, we characterize the HNO cells and their biological attributes against those of the parent cells. Pairs of HNO/parent cell lines were then analyzed using a number of key cellular activity criteria including: cell cycle distribution, DNA ploidy, response to DNA damage, UV radiation response, X-ray radiation response, and the expression of significant cellular enzymes. Other key enzyme activities studied were NOS, p53, and glutathione S-transferase-pi (GST-pi) expression. HNO cells were typified by a far more aggressive pattern of growth and resistance to various treatments than the corresponding parent cells. This was evidenced by a higher S-phase percentage, variable radioresistance, and up-regulated GST-pi and p53. Taken collectively, this data provides evidence that cancer cells subjected to HNO concentrations become resistant to free radicals such as NO via up-regulated cellular defense mechanisms, including p53 and GST-pi. The

show abstract

Nitric oxide: A cytotoxic activated macrophage effector molecule

Cited by 1,897 publications

References 25 publications

Inhibition of nitric oxide synthase by nasal decongestants

Inhibition of nitric oxide synthase by nasal decongestants

Nitric oxide and arthritis

Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines

Contact Info

Product

Resources

About