Macrophage VLDL Receptor Promotes PAFAH Secretion in Mother’s Milk and Suppresses Systemic Inflammation in Nursing Neonates

Abstract

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 receptor (VLDLR) deletion in mice causes the production of defective milk containing diminished level of platelet-activating factor acetylhydrolase (PAFAH). As a consequence, the nursing neonates suffer from alopecia, anemia and growth retardation owing to elevated levels of pro-inflammatory platelet-activating factors (PAFs). VLDLR 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 VLDLR in suppressing inflammation by maintaining macrophage PAFAH secretion, but also identify the maternal VLDLR as a key genetic program that ensures milk quality and protects the newborns.