Abstract
Acute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic defense against pathogens as well as pathologies including autoimmunity and cancer. A major mechanism through which neutrophils contribute to health and disease is oxidative burst, which involves rapid release of reactive oxygen species (ROS) generated by a chemical reaction network catalyzed by enzymes including NADPH oxidase and myeloperoxidase (MPO). Due to the involvement of neutrophil-derived reactive oxygen species in many diseases and importance of NADPH oxidase and MPO-mediated reactions in progression and treatment of myeloid leukemia, monitoring this process and modulating it by pharmacological interventions is of great interest. In this work, we have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor ROS production in neutrophil-like HL60 myeloid leukemia cells. Suppression of ROS was achieved by several drug candidates that target different parts of the reaction pathway. Our results show that UPE can report on ROS production as well as suppression by pharmacological inhibitors. We find that UPE is primarily generated by MPO catalyzed reaction and thus will be affected when an upstream reaction is pharmacologically modulated.
Highlights
Innate immune cells are key to health and many diseases
We have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor reactive oxygen species (ROS) production in neutrophil-like HL60 myeloid leukemia cells
We find that Acute myeloid leukemia (AML) cells generate a weak UPE signal in resting state and this signal is amplified when the cells are treated with phorbol 12-myristate 13-acetate (PMA) [28]
Summary
Neutrophil granulocytes ( called neutrophils), the most abundant innate immune cells, are at the forefront to fight against infections, regulate the adaptive immune system, and contribute to tissue damage when activated in excess [1,2,3,4]. The rapid release of superoxide anion radicals (O2·-) and hydrogen peroxide (H2O2), which are the primary source of the oxidants, is followed by rapid conversion into other oxidant species (OH·, HOCl, etc) [5]. These processes are catalyzed mainly by two enzymes, NADPH oxidase and myeloperoxidase (MPO), the latter being a signature protein of neutrophils. ROS production is beneficial at right doses; the overproduction of ROS (usually called as oxidative stress) has been related to several disorders such as Alzheimer’s disease [6], Parkinson’s disease [7], cancer [8, 9], cardiovascular www.impactjournals.com/oncotarget diseases [10] and chronic diseases such as diabetes [11], and rheumatoid arthritis [12]
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