Macrophage VLDL receptor promotes PAFAH secretion in mother's milk and suppresses systemic inflammation in nursing neonates

Nat Commun. 2012:3:1008. doi: 10.1038/ncomms2011.


Mother's milk is widely accepted as nutritious and protective to the newborn mammals by providing not only macronutrients but also immune-defensive factors. However, the mechanisms accounting for these benefits are not fully understood. Here we show that maternal very-low-density-lipoprotein (VLDL) receptor deletion in mice causes the production of defective milk containing diminished levels of platelet-activating factor acetylhydrolase (PAFAH). As a consequence, the nursing neonates suffer from alopecia, anaemia and growth retardation owing to elevated levels of pro-inflammatory platelet-activating factors. VLDL receptor deletion significantly impairs the expression of phospholipase A2 group 7 (Pla2g7) in macrophages, which decreases PAFAH secretion. Exogenous oral supplementation of neonates with PAFAH effectively rescues the toxicity. These findings not only reveal a novel role of VLDL receptor in suppressing inflammation by maintaining macrophage PAFAH secretion, but also identify the maternal VLDL receptor as a key genetic program that ensures milk quality and protects the newborns.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Animals
  • Animals, Newborn / immunology
  • Breast Feeding*
  • Down-Regulation*
  • Female
  • Humans
  • Infant, Newborn / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk / enzymology*
  • Milk / immunology
  • Neonatal Nursing
  • Phospholipases A2 / genetics
  • Phospholipases A2 / immunology
  • Phospholipases A2 / metabolism*
  • Platelet Activating Factor / immunology
  • Protein Transport
  • Receptors, LDL / genetics
  • Receptors, LDL / immunology*


  • Platelet Activating Factor
  • Receptors, LDL
  • VLDL receptor
  • Phospholipases A2
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Pla2g7 protein, mouse