Alpha-Lactalbumin in Human Milk Alters the Proteolytic Degradation of Soluble CD14 by Forming a Complex

• Published in: Pediatric research Vol. 68; no. 6; pp. 490 - 493
• Main Authors: Spencer, William J, Binette, Andrew, Ward, Tonya L, Davis, Laura D R, Blais, David R, Harrold, Joann, Mack, David R, Altosaar, Illimar
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-12-2010; Lippincott Williams & Wilkins
• Subjects: Adult; Animals; basic-science-investigation; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gastrointestinal Tract - chemistry; Gastrointestinal Tract - metabolism; General aspects; Humans; Infant, Newborn; Lactalbumin - chemistry; Lactalbumin - metabolism; Lipopolysaccharide Receptors - administration & dosage; Lipopolysaccharide Receptors - chemistry; Lipopolysaccharide Receptors - metabolism; Mass Spectrometry; Medical sciences; Medicine; Medicine & Public Health; Milk, Human - chemistry; Mother. Fetoplacental unit. Mammary gland. Milk; Multiprotein Complexes - metabolism; Pediatric Surgery; Pediatrics; Pregnancy. Parturition. Lactation; Rats; Rats, Sprague-Dawley; Vertebrates: reproduction; Pediatrics; Rat; Digestive system; Rodentia; Soluble form; Vertebrata; Mammalia; Lactalbumin; Proteolysis; Newborn animal; Human milk; Biological effect; Digestive tract
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/PDR.0b013e3181f70f21

Mother's milk represents a foundational step in the proper development of newborn immunity. This is achieved, in part, through the action of numerous regulatory proteins such as soluble cluster of differentiation 14 (sCD14) found in significant quantities in human milk (∼25–50 μg/mL). In adults, CD14 stimulates cytokine production in response to lipopolysaccharide (LPS), the major lipid component found in the outer membrane of Gram-negative bacteria. However, the fate and function of sCD14 in the neonatal gastrointestinal (GI) tract are unknown and may function differently from adults. Therefore, we administered human sCD14 to experimental animals and observed that it persisted in the upper GI tract after feeding. In our search for potential proteolytic protectants, immunoprecipitation of sCD14 from human milk revealed a 15-kD novel protein that copurified with sCD14. Mass spectrometry analysis of the protein identified alpha-lactalbumin. CD14 was also identified by immunoblot after immunoprecipitation of alpha-lactalbumin from milk.
In vitro
digestion assays revealed that purified alpha-lactalbumin decreases the proteolytic degradation of human milk derived sCD14
in vitro
, suggesting a mechanism by which this key LPS receptor may remain functional in the neonate gut.