Human Milk and the Response of Intestinal Epithelium to Infection

Bernt, Kathrin M.; Walker, W. Allan

doi:10.1007/978-1-4615-1371-1_2

Cited by 12 publications

(9 citation statements)

References 88 publications

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“…(20) Interestingly, lysozyme also evolved various nutritional roles in the mammary gland. Over evolutionary time, lysozyme underwent gene duplications and the duplicated allele evolved into a-lactalbumin, an important nutritional whey protein unique to the lactating mammary gland.…”

Section: Introductionmentioning

confidence: 99%

Evolution of the mammary gland from the innate immune system?

2006

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The mammary gland is a skin gland unique to the class Mammalia. Despite a growing molecular and histological understanding of the development and physiology of the mammary gland, its functional and morphological origins have remained speculative. Numerous theories on the origin of the mammary gland and lactation exist. The purpose of the mammary gland is to provide the newborn with copious amounts of milk, a unique body fluid that has a dual role of nutrition and immunological protection. Interestingly, antimicrobial enzymes, such as xanthine oxidoreductase or lysozyme, are directly involved in the evolution of the nutritional aspect of milk. We outline that xanthine oxidoreductase evolved a dual role in the mammary gland and hence provide new evidence supporting the hypothesis that the nutritional function of the milk evolved subsequent to its protective function. Therefore, we postulate that the mammary gland evolved from the innate immune system. In addition, we suggest that lactation partly evolved as an inflammatory response to tissue damage and infection, and discuss the observation that the two signaling pathways, NF-kB and Jak/Stat, play central roles in inflammation as well as in lactation.

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Section: Introductionmentioning

confidence: 99%

Evolution of the mammary gland from the innate immune system?

2006

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“…Mammalian milk is composed of mammary gland products and serum components that passively diffuse to it (Jensen, 1995). It supplies the newborn with nutrients, enzymes, growth factors, and hormones, as well as protection against infections (Howie et al, 1990;Jensen, 1995;Cesar et al, 1999;Bernt and Walker, 2001). The latter is mainly provided by secretory immunoglobulins, lipids, and oligosaccharides (free and conjugated to macromolecules, including proteins; Wold et al, 1990;Hennart et al, 1991;Hamosh, 1998).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa Lectin PA-IIL as a Powerful Probe for Human and Bovine Milk Analysis

Lesman-Movshovich

Gilboa‐Garber

2003

Journal of Dairy Science

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Milk composition exhibits species-specific differences depending on genetic, evolutionary, and environmental factors. In addition, commercial milk preparations are also changed by industrial manipulations, including severe heat processing. Cow milk, used as human food, provides important nutrients but lacks some essential components that are present in raw human milk. The present study, which was aimed at comparing infant breastfeeding to cow-based formula nourishment, shows major differences between the human and the commercial cow milk glycans detectable by the lectins PA-IL (galactose-binding) and PA-IIL (fucose and mannose-binding) isolated from the cells of human pathogen Pseudomonas aeruginosa. More than 40 human milk samples, several cow milks, and bovine milk-based infant formulas, were examined using these two lectins. For purposes of comparison, the plant lectins Concanavalin A (Con A), which binds mannose, and Ulex europaeus 1st lectin (UEA-I), which binds fucose, were also used. The most prominent difference was revealed using PA-IIL, which displayed a unique high sensitivity to the human milk fucosylated compounds. PA-IL and UEA-I also exhibited preferential sensitivity to the human milk but considerably lower than that of PA-IIL. Con A was inhibited by human and the other milk preparations examined to the same extent. These findings indicate the superb applicability of PA-IIL for rapid and reliable comparative investigation of milk glycans from human and cow, indicating which glycans could be added to infant formulas in order to enrich them, as well as for verification and quality control of otherwise improved bovine milk-based infant formulas.

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“…Unlike the adaptive immune system, which depends on specialized immune cells, the innate immune system is primarily mediated by peptides, small proteins, and enzymes that are mainly secreted from exocrine glands. It has been reported that animal milk contains epithelial‐derived peptides such as lysozyme, α‐lactalbumin, lactoperoxidase, xanthine oxidoreductase, and defensins, in addition to proinflammatory cytokines from immune cells that exhibit antibacterial activity as part of the innate immune defense system in the mammary glands (7–9). However, it remains to be elucidated whether these proteins actually function in mammary glands.…”

mentioning

confidence: 99%

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

Nagaoka

Aoki²,

Hayashi

et al. 2009

FASEB j.

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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.

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Human Milk and the Response of Intestinal Epithelium to Infection

Cited by 12 publications

References 88 publications

Evolution of the mammary gland from the innate immune system?

Evolution of the mammary gland from the innate immune system?

Pseudomonas aeruginosa Lectin PA-IIL as a Powerful Probe for Human and Bovine Milk Analysis

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

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