Macrophage VLDL receptor promotes PAFAH secretion in mother's milk and suppresses systemic inflammation in nursing neonates.
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.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Yang
Y
Du
Marie
M
Yang
Wei
W
Wei
Hoang Dinh
HD
Huynh
Joachim
J
Herz
Alan
A
Saghatelian
Yihong
Y
Wan
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001942:Breast Feeding; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008892:Milk / Q000201:enzymology* / Q000276:immunology; D017283:Neonatal Nursing; D054467:Phospholipases A2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000276:immunology; D021381:Protein Transport; D011973:Receptors, LDL / Q000235:genetics / Q000276:immunology*
D010972:Platelet Activating Factor; D011973:Receptors, LDL; C036053:VLDL receptor; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C571209:Pla2g7 protein, mouse