Effects of ornithine 2-oxoglutarate on neutrophils in stressed rats: evidence for the involvement of nitric oxide and polyamines

Diets enriched in ornithine 2-oxoglutarate (ornithine α-ketoglutarate; OKG) improve immune status during stress. We described previously the ability of OKG to increase the respiratory burst in polymorphonuclear neutrophils (PMNs), but the underlying mechanisms remain unclear. OKG is usually recognized as generating glutamine, arginine and polyamines. The aim of the present study was first to determine the effects of OKG on PMN bactericidal functions (chemotaxis and respiratory burst) in stressed rats, and whether these effects could be reproduced by glutamine- or arginine-enriched diets. Secondly, we investigated the metabolic pathway involved in these actions, using three metabolic inhibitors: methionine sulphoximine (an inhibitor of glutamine synthetase), S-methylthiourea (an inhibitor of inducible nitric oxide synthase) and difluoromethylornithine (an inhibitor of ornithine decarboxylase). OKG, arginine and glutamine all increased the production of reactive oxygen species (evaluated by chemiluminescence, ferricytochrome c reduction and flow cytometry). Only OKG markedly enhanced the chemotaxis index (5-fold). Inhibition of glutamine synthetase showed that glutamine production was not involved in the action of OKG. The use of S-methylthiourea and difluoromethylornithine demonstrated that OKG modulated the respiratory burst via nitric oxide (NO·) and polyamine generation. Moreover, OKG stimulated PMN migration via NO·, but arginine administration failed to reproduce this effect. These data suggest that OKG (or its metabolites) and arginine are channelled differently in PMNs. This hypothesis deserves further study.

Download Full-text

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180426121503 ◽

2018 ◽

Vol 16 (2) ◽

pp. 194-199

Author(s):

Wioletta Ratajczak-Wrona ◽

Ewa Jablonska

Keyword(s):

Nitric Oxide ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Polymorphonuclear Neutrophils ◽

Microbial Pathogens ◽

Human Neutrophils ◽

No Production ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Download Full-text

Distribution of CD14+ macrophages, CD4+, CD8+ lymphocytes and mRNA expression of inducible nitric oxide synthase in the endometrium of repeat breeding cows

Polish Journal of Veterinary Sciences ◽

10.2478/pjvs-2013-0062 ◽

2013 ◽

Vol 16 (3) ◽

pp. 443-451 ◽

Cited By ~ 1

Author(s):

W. Barański ◽

J. Kaleczyc ◽

S. Zduńczyk ◽

W. Podlasz ◽

E. Długołęcka-Malinowska ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Mrna Expression ◽

Inducible Nitric Oxide Synthase ◽

Polymorphonuclear Neutrophils ◽

Control Group ◽

Inos Mrna ◽

Oxide Synthase ◽

Subclinical Endometritis ◽

Inducible Nitric Oxide

Abstract The expression of CD14+ macrophages, CD4+, CD8+ lymphocytes and mRNA of inducible nitric oxide synthase (iNOS) was investigated in the endometrium of repeat breeders with subclinical endometritis [experimental group (EXP), n = 10] and healthy [control group (CTRL), n = 10] cows. The cows were selected on the basis of repeat breeding (3 unsuccessful inseminations), clinical and cytological examinations (> 10% polymorphonuclear neutrophils in uterine smears obtained by cytobrush). From all the cows endometrial biopsies were collected and the presence of CD14+, CD4+ and CD8+ cells in the endometrium was evaluated immunohistochemically using semi quantitative counting method. The mRNA expression of iNOS was determined using reverse transcription-PCR. In general, there were no significant differences between EXP and CTRL groups in the expression of CD4+ and CD8 + lymphocytes in all endometrial structures. In contrast, we observed a higher number of CD14+ macrophages in repeat breeding group compared to the control cows, however, this difference was slightly pronounced. CD14+ cells were detectable only in the stratum compactum and stratum spongiosum. The statistically significant (p ≤ 0.05) higher expression of iNOS mRNA was measured in the cows with subclinical endometritis compared to the healthy animals. Our results suggest that the increased expression of CD14+ macrophages and iNOS mRNA may be associated with embryonal mortality in repeat breeding cows with subclinical endometritis.

Download Full-text

Cloning of an Inducible Nitric Oxide Synthase from Rat Polymorphonuclear Neutrophils

Endothelium ◽

10.3109/10623329409053378 ◽

1994 ◽

Vol 2 (3) ◽

pp. 217-221 ◽

Cited By ~ 10

Author(s):

Kunihiko Kosuga ◽

Yoshiki Yui ◽

Ryuichi Hattori ◽

Kazuhiro Sase ◽

Hiroshi Eizawa ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Polymorphonuclear Neutrophils ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Download Full-text

Female’s Heightened Immune Status: Estrogen, T Cells, and Inducible Nitric Oxide Synthase in the Balance

Endocrinology ◽

10.1210/en.2005-1469 ◽

2006 ◽

Vol 147 (2) ◽

pp. 659-661 ◽

Cited By ~ 24

Author(s):

Daniela Verthelyi

Keyword(s):

Nitric Oxide ◽

T Cells ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Immune Status ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Download Full-text

Sex-specific differences in the regulation of inducible nitric oxide synthase by bisphenol A in neutrophils

Human & Experimental Toxicology ◽

10.1177/0960327118793188 ◽

2018 ◽

Vol 38 (2) ◽

pp. 239-246 ◽

Cited By ~ 7

Author(s):

W Ratajczak-Wrona ◽

K Nowak ◽

M Garley ◽

M Tynecka ◽

E Jablonska

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Bisphenol A ◽

Inducible Nitric Oxide Synthase ◽

Polymorphonuclear Neutrophils ◽

No Production ◽

Nuclear Fraction ◽

Oxide Synthase ◽

Inducible Nitric Oxide ◽

Stimulation Of

The aim of the study was to evaluate the effect of bisphenol A (BPA) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by neutrophils with regard to sex and nuclear factor-κB (NF-κB) pathway participation in this process. This study demonstrated that BPA intensifies the production of NO and the expression of iNOS in the cytoplasmic fraction of neutrophils of women as well as men. In addition, an enhanced expression of NF-κB in the cytoplasmic and nuclear fraction of neutrophils exposed to BPA was observed in the cells of both sexes. The lipopolysaccharide (LPS) stimulation of neutrophils of both sexes led to an intensification of NO production and expression of all tested proteins. However, simultaneous stimulation of neutrophils of both men and women with LPS and BPA decreased the production of NO and expression of iNOS and NF-κB in both fractions compared to the cells exposed only to xenoestrogen. Moreover, expression of iNOS and NF-κB was higher in female neutrophils than in male cells. This study demonstrated that BPA affects the production of NO with the participation of iNOS by human polymorphonuclear neutrophils. This process is associated with the activation of the NF-κB pathway. In addition, different activity of NF-κB in neutrophils, observed with respect to sex, indicates a different role of this pathway in female and male cells.

Download Full-text