Killing the Messenger in the Nick of Time: Persistence of Breast Milk sCD14 in the Neonatal Gastrointestinal Tract

Blais, David R.; Harrold, JoAnn; Altosaar, Illimar

doi:10.1203/01.pdr.0000199907.61549.94

Cited by 31 publications

(37 citation statements)

References 37 publications

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“…Previous work from our laboratory has demonstrated that human milk-derived sCD14 is not detectable in the stool of newborn breast-fed infants and is adsorbed, sequestered, or degraded (25). In combination with the present results, sCD14 is still observed to be sensitive to proteolysis; however, the presence of a resistant pool in the stomach does not preclude the possibility of CD14 degradation further along the GI tract.…”

Section: Discussionsupporting

confidence: 74%

“…In vitro digests using trypsin alone or in combination with chymotrypsin and pancreatin were performed to investigate whether such a complex alters CD14 stability. The sCD14 from human milk is known to be proteolytically resistant to pepsin digestion and partially resistant to pancreatin digestion in vitro (25). The present results show that a higher concentration of trypsin is required to completely digest CD14 in the presence of alpha-lactalbumin than the control protein, lysozyme (Fig.…”

Section: Resultsmentioning

confidence: 51%

“…1) suggests that sCD14 complexed with alphalactalbumin may permit sCD14 to migrate further along the GI tract than would be possible in the absence of this interaction. Therefore, sCD14 and alpha-lactalbumin occupy a specific temporal window during infant development, most notably after birth when the child begins feeding from the breast, and sCD14 levels are at their highest concentration in human milk (25,31,32). This suggests that early colonization of the gut and the presence of sCD14/alpha-lactalbumin complexes may be a coordinated process to ensure population by appropriate commensal microbes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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ABSTRACT: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 (ϳ25-50 g/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 alphalactalbumin 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.

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Section: Discussionsupporting

confidence: 74%

Section: Resultsmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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“…Second, the effects caused by colostral factors may no longer be valid at the infant's age of 1 month because the permeability of the gut is diminishing and the efficiency of proteolysis is enhanced [37]. In addition, Blais et al [38] found that sCD14 in breast milk is more susceptible to the infant's pancreatin digestion vs. pepsin digestion by in vitro experiments, suggesting decreased activity of sCD14 in the LPS-rich environment of the distal bowel. Third, the use of different ELISA kits may explain inconsistent results between studies [23].…”

Section: Discussionmentioning

confidence: 99%

Cytokines and soluble CD14 in breast milk in relation with atopic manifestations in mother and infant (KOALA Study)

Snijders

Damoiseaux²,

Penders

et al. 2006

Clin Experimental Allergy

113

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SummaryBackground Conflicting evidence exists concerning the protective role of breastfeeding in allergy and atopic disease aetiology. Breast milk contains biologically active molecules influencing the innate immune system of newborns. Objective We aim to assess whether cytokines (TGF-b1, IL-10 and IL-12) and soluble CD14 (sCD14) in breast milk are influenced by maternal atopic constitution and modify the development of atopic manifestations in infants. Methods Milk samples were collected at 1 month post-partum of 315 lactating mothers participating in the ongoing KOALA Birth Cohort Study. The cytokines and sCD14 were analysed by ELISA in the aqueous fraction. We compared the concentrations of cytokines and sCD14 in breast milk between mothers with and without an allergic history and also with and without allergic sensitization (specific IgE). Associations of cytokines and sCD14 with the development of eczema, wheezing in the first 2 years of life and allergic sensitization of infants at the age of 2 years were analysed by multivariate logistic regression analyses to correct for confounders. Results We found higher sCD14 levels in mothers with a positive vs. negative allergic history (7.6 vs. 7.0 mg/mL; P = 0.04) and in mothers who were sensitized vs. non-sensitized (7.8 vs. 7.1 mg/mL; P = 0.03). None of the studied immune factors were associated with infant's atopic outcomes. IL-10 was not detected above the detection limit of 0.2 pg/mL. Conclusion Taking together the results of the present and previous studies, we conclude that there is no convincing evidence for a relation between TGF-b1, sCD14, IL-10 or IL-12 in breast milk and atopic manifestations in infants.

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“…The observation that breast milk sCD14 survives intact in conditions that mimic the upper digestive tract but is digested by pancreatin (Blais et al, 2006) suggests that such innate responses are initiated in an environment with low bacterial density but are avoided in the densely populated distal intestine.…”

Section: Relevance Of Scd14 For Infant Healthmentioning

confidence: 99%

CD14: A Soluble Pattern Recognition Receptor in Milk

Vidal

Donnet-Hughes

Advances in Experimental Medicine and Biology

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An innate immune system capable of distinguishing among self, non-self, and danger is a prerequisite for health. Upon antigenic challenge, pattern recognition receptors (PRRs), such as the Toll-like receptor (TLR) family of proteins, enable this system to recognize and interact with a number of microbial components and endogenous host proteins. In the healthy host, such interactions culminate in tolerance to self-antigen, dietary antigen, and commensal microorganisms but in protection against pathogenic attack. This duality implies tightly regulated control mechanisms that are not expected of the inexperienced neonatal immune system. Indeed, the increased susceptibility of newborn infants to infection and to certain allergens suggests that the capacity to handle certain antigenic challenges is not inherent. The observation that breast-fed infants experience a lower incidence of infections, inflammation, and allergies than formula-fed infants suggests that exogenous factors in milk may play a regulatory role. There is increasing evidence to suggest that upon exposure to antigen, breast milk educates the neonatal immune system in the decision-making processes underlying the immune response to microbes. Breast milk contains a multitude of factors such as immunoglobulins, glycoproteins, glycolipids, and antimicrobial peptides that, qualitatively or quantitatively, may modulate how neonatal cells perceive and respond to microbial components. The specific role of several of these factors is highlighted in other chapters in this book. However, an emerging concept is that breast milk influences the neonatal immune system's perception of "danger." Here we discuss how CD14, a soluble PRR in milk, may contribute to this education.

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Killing the Messenger in the Nick of Time: Persistence of Breast Milk sCD14 in the Neonatal Gastrointestinal Tract

Cited by 31 publications

References 37 publications

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

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

Cytokines and soluble CD14 in breast milk in relation with atopic manifestations in mother and infant (KOALA Study)

CD14: A Soluble Pattern Recognition Receptor in Milk

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