Regulation of Polyamine Synthesis and Transport in the Context of Macrophage Polarization and Pathogen Invasion
- Author(s): Gil, Jacqueline Michelle
- Advisor(s): Carson, Monica J.
- et al.
Macrophages play a vital role in early defense against pathogens and are required for tissue repair following injury. In response to various stimuli, macrophages become activated/polarized towards pro-inflammatory or anti-inflammatory states, known as M1 and M2 states respectively. Arginase1 (Arg1), the most commonly used diagnostic marker of M2 macrophage polarization, is also the enzyme that catalyzes arginine into ornithine, which feeds into the polyamine biosynthetic pathway. Polyamines, positively charged, organic aliphatic compounds; are necessary for cell growth and survival in all living organisms. In M1/M2 macrophages, arginine/polyamine synthesis and transport are tightly regulated. Higher intracellular levels of polyamines can promote tumor formation in cells where mutations have already occurred. Still, the mechanisms underlying the control of these responses in the context of the polyamine metabolism have not been completely elucidated. When Arg 1 expression is upregulated, it is expected that the synthesis and export of polyamines will subsequently increase. Yet, it is still not clear if polyamines serve a physiological function in M2 macrophages or are merely bystanders in the entire M2 macrophage activation/ polarization process. The usage of novel polyamine synthesis inhibitors provides a useful approach to understanding the role of polyamines in both macrophage states. The inhibition of polyamine synthesis has been used as a treatment for pathogen invasion, because many pathogens rely on arginine and polyamines for growth and survival. In other words, arginine/polyamines are not only indispensible resources for their hosts, but also for the pathogens that prey upon them.