L‐Amino acid oxidase plays a crucial role in host defense in the mammary glands

Abstract

The innate immune system plays an important role in protecting organs that are continuous with the outer surface of the body from bacterial infection. The antibacterial factors involved in this system have been sought in exocrine glands, particularly in the mammary glands. Because milk produced in the mammary glands is enriched in various nutrients, supporting the proliferation of bacteria, mammary glands appear to be at the greatest risk of bacterial infection and proliferation. Here, we show that mouse milk contains L-amino acid oxidase (LAO), a lactating mammary gland-specific protein that displays antibacterial activity in vitro through the production of hydrogen peroxide from free amino acids. We produced LAO-disrupted mouse lines to define the physiological properties and importance of the protein in vivo. The LAO-knockout mice were healthy and had normal mammary gland development; however, the antibacterial activity normally observed in milk from wild-type mice was absent from the milk of knockout mice. The content of free amino acids targeted by LAO was very low in wild-type milk, whereas these amino acids were abundant in LAO-knockout milk. Knockout mice exhibited weak resistance to an intramammary bacterial challenge compared to their wild-type counterparts. Further, preadministration of wild-type milk whey reduced the severity of bacterial infection in LAO-knockout mice. These results demonstrate that milk LAO protects the mammary gland against bacterial infection, and this antibacterial effect may be due to the generation of hydrogen peroxide by using free amino acids abundantly present in milk.

Antibacterial properties of l-amino acid oxidase: mechanisms of action and perspectives for therapeutic applications

“…Mouse milk contains LAAO, a lactating mammary gland-specific protein, which also displays antibacterial activity against E. coli and S. aureus through the production of hydrogen peroxide from free amino acids in milk (Nagaoka et al 2009). These reports suggest that human IL4I1 and LAAO containing mouse milk play an important role in protecting organs from bacterial infection by the innate immune systems.…”

The serum of rabbitfish (Siganus oramin) has antimicrobial activity to some pathogenic organisms and a novel serum l-amino acid oxidase is isolated

“…Moreover, they are widely distributed across diverse phyla from bacteria to mammals, which appear to be important in both vertebrate and invertebrate host defenses [9]. Most of the antibacterial LAAOs reported to date derived from secretory glands, such as venom in snakes [10e13], body surface mucous secretion in terrestrial snails [9], the albumen gland and ink in sea hares [14e16], epidermal mucus in fish [17e19], and milk in mice [20,21]. It was first reported in teleost fish by Jung et al (2000) that the presence of LAAO as an apoptosis inducing protein (AIP) in Mackerel viscera infected with the nematode Anisakis simplex [22].…”

Transcriptomic analysis reveals key regulators of mammogenesis and the pregnancy-lactation cycle

“…Cel participates in chylomicron assembly and secretion in a mechanism mediated through its ceramide hydrolytic activity [40]. Other up-regulated genes such as Lao and Qsox encode antibacterial activity in their respective products through the production of hydrogen peroxide [41] and via a secretory function during mammary cell differentiation [42,43]. For the most significant top 10 down-regulated genes, alveolar ductal proliferation and cell differentiation were apparently inhibited, while cell motion and cell communication were also less active during lactation.…”