Xanthine oxidase-lactoperoxidase system and innate immunity: Biochemical actions and physiological roles

Abstract

The innate immune system in mammals is the first-line defense that plays an important protective role against a wide spectrum of pathogens, especially during early life before the adaptive immune system develops. The enzymes xanthine oxidase (XO) and lactoperoxidase (LPO) are widely distributed in mammalian tissues and secretions, and have a variety of biological functions including in innate immunity, provoking much interest for both in vitro and in vivo applications. The enzymes are characterized by their generation of reactive oxygen and nitrogen species, including hydrogen peroxide, hypothiocyanite, nitric oxide, and peroxynitrite. XO is a major generator of hydrogen peroxide and superoxide that subsequently trigger a cascade of oxidative radical pathways, including those produced by LPO, which have bactericidal and bacteriostatic effects against pathogens including opportunistic bacteria. In addition to their role in host microbial defense, reactive oxygen and nitrogen species play important physiological roles as second messenger cell signaling molecules, including cellular proliferation, differentiation and gene expression. There are several indications that the reactive species generated by peroxide have positive effects on human health, particularly in neonates; however, some important in vivo aspects of this system remain obscure. The primary dependence of the system on hydrogen peroxide has led us to propose it is particularly relevant to neonate mammals during milk feeding.

Keywords: Cell signaling; Innate immunity; Lactoperoxidase; Reactive oxygen species; Xanthine oxidase.

Fig. 1

The major XO-LPO system pathway and metabolism. XDH is synthesized but then converted to XO during secretion, in the milk fat globule membrane (MFGM). The system is associated with a wide range of antimicrobial () ROS and RNS. The system is triggered by its main substrates, which include the purines hypoxanthine/xanthine, thiocyanate, nitrates, and nitrites.