PMID- 19276171
OWN - NLM
STAT- MEDLINE
DCOM- 20090818
LR  - 20120215
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 8
DP  - 2009 Aug
TI  - L-amino acid oxidase plays a crucial role in host defense in the mammary glands.
PG  - 2514-20
LID - 10.1096/fj.08-126466 [doi]
AB  - 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.
FAU - Nagaoka, Kentaro
AU  - Nagaoka K
AD  - Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, 
      University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. 
      akenaga@mail.ecc.u-tokyo.ac.jp
FAU - Aoki, Fugaku
AU  - Aoki F
FAU - Hayashi, Mizuna
AU  - Hayashi M
FAU - Muroi, Yoshikage
AU  - Muroi Y
FAU - Sakurai, Toshihiro
AU  - Sakurai T
FAU - Itoh, Kikuji
AU  - Itoh K
FAU - Ikawa, Masahito
AU  - Ikawa M
FAU - Okabe, Masaru
AU  - Okabe M
FAU - Imakawa, Kazuhiko
AU  - Imakawa K
FAU - Sakai, Senkiti
AU  - Sakai S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090310
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - EC 1.4.3.2 (L-Amino Acid Oxidase)
SB  - IM
MH  - Animals
MH  - Bacterial Infections/enzymology/immunology/prevention & control
MH  - Female
MH  - *Immunity, Innate
MH  - L-Amino Acid Oxidase/deficiency/genetics/*immunology
MH  - Lactation/immunology/metabolism
MH  - Mammary Glands, Animal/*enzymology/*immunology/microbiology
MH  - Mastitis/enzymology/immunology/prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Milk/chemistry/enzymology/immunology
MH  - Staphylococcal Infections/enzymology/immunology/prevention & control
MH  - Staphylococcus aureus/immunology/pathogenicity
EDAT- 2009/03/12 09:00
MHDA- 2009/08/19 09:00
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/08/19 09:00 [medline]
AID - fj.08-126466 [pii]
AID - 10.1096/fj.08-126466 [doi]
PST - ppublish
SO  - FASEB J. 2009 Aug;23(8):2514-20. doi: 10.1096/fj.08-126466. Epub 2009 Mar 10.