New insight into the NO-mediated signaling to modulate neutrophil free radical generation

Patel, Satyananda ; Kumar, Sachin ; Barthwal, Manoj Kumar ; Dikshit, Madhu (2007) New insight into the NO-mediated signaling to modulate neutrophil free radical generation The FASEB Journal, 21 . pp. 638-644. ISSN 0892-6638

Full text not available from this repository.

Official URL:


Neutrophils (PMNs) and nitric oxide (NO) play an important role in pathogen killing as well as in various pathological conditions associated with inflammation, hypoxia/ischemia and reoxygenation injury by generating reactive oxygen (ROS) and reactive nitrogen (RNS) species. Previous work from this lab has shown that NO modulates neutrophil NADPH-oxidase (NOX) activity and thus modulates ROS production. The present study has been undertaken to assess signalling mechanisms involved in NO mediated effect on PMNs by flowcytometry (DCF-DA, DHE, propidium iodide, CBA Flex array), biochemical (H2O2, hypochlorous acid [HOCl], nitryl chloride [NO2Cl], dityrosine) and molecular (Western blotting) measurements. NO donors, SNP and SNAP (10 µM to 1 mM) inhibited the NADPH-oxidase activity but enhanced DCF-DA fluorescence in a concentration and time dependent manner, with no adverse effect on the cell viability. The effect was significantly blocked by NOS inhibitors and was partially blocked by ERK and MPO inhibitors. NO at the concentrations used seems to activate futile cycle generating peroxynitrite (ONOO)/NO3, which subsequently uncouples NOS and generate superoxide radicals and H2O2. H2O2 thus formed leads to the formation of HOCl by MPO catalysis, which further reacts with nitrite (NO2) to generate NO2Cl, a more potent oxidant and nitrating agent. The results obtained thus suggest that NO mediated augmentation in neutrophil free radical production involves ERK signalling.

Item Type:Article
Source:Copyright of this article belongs to The Federation of American Societies for Experimental Biology.
ID Code:89078
Deposited On:30 Mar 2012 10:39
Last Modified:30 Mar 2012 10:39

Repository Staff Only: item control page