Arginase: A Prospective Regulator of Oxidative Stress During Microbial Pathogenesis
Arginase is a manganese metalloenzyme that regulates the intracellular availability of L-arginine through its hydrolysis to urea and L-ornithine. Arginine is a common substrate for both nitric oxide synthase (NOS) and arginase. L-Arginine converted to nitric oxide (NO) and L-ornithine by nitric oxide synthase. Nitric oxide (NO) initiates the immunomodulatory effects within host and imparts defense by inducing microbicidal activity against invading pathogens within the cellular microenvironment. Therefore, the competition between arginase and nitric oxide synthase for arginine plays a determinant role in immune response against microbial pathogenesis. It was reported that depletion of arginine by myeloid cells expressing arginase 1 leads to suppression of T-cell immune response. Pathogens themselves were found to synthesize arginase to escape host immune response. Recent research has identified that reactive oxygen species (ROS) plays a significant role in the regulation of arginase activity and expression during microbial infection. Pathogen survival within the host system depends on the inclination to arginase pathway. Moreover, arginase participates in arginine metabolism which provides an essential route for sustainability of pathogen survival and reproduction within the host by negotiating host defense response. Researchers currently have shown that arginase modulates the host immune response and infection pathology in many ways during microbial, parasitic, and also viral infections. In this chapter, we have discussed about the involvement of arginase in the modulation of NO during inflammatory response coined by host upon encounter to pathogen. We have highlighted the involvement of arginase in the modulation of host immune response during bacterial, viral, and parasitic infection. The current and potential therapeutic approaches against microbial diseases by targeting arginase function were discussed.
KeywordsArginases iNOS Polyamines Macrophages Immune response Host-pathogen interactions
The author acknowledges the support of Ms. Trishna Mahanty and Dr. Avik Sarkar in the preparation of the manuscript. Indian government extramural research funds from Indian Council of Medical Research and SERB-Department of Science and Technology to author’s laboratory are sincerely acknowledged.
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