Glycoproteins of the Human Milk Fat Globule in the Protection of the Breast-Fed Infant against Infections

Peterson, Jerry A.; Patton, Stuart; Hamosh, Margit

doi:10.1159/000014020

Cited by 138 publications

(100 citation statements)

References 48 publications

(88 reference statements)

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“…23,24 The homology of the lactadherin C domains with those of factors VIII and V suggests that similar phospholipid-binding properties may exist. Indeed, lactadherin has been found to bind selectively to PS 25 and to use primarily the C2 domain in its lipid binding. 6 Annexin V, like factor VIII and factor V, exhibits high-affinity, PS-dependent membrane binding.…”

Section: Introductionmentioning

confidence: 99%

Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites

Shi

Gilbert

2003

Blood

161

151

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Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C domains with homology to discoidin-type lectins and to membrane-binding domains of blood-clotting factors V and VIII. We asked whether the structural homology confers the capacity to compete for the membrane-binding sites of factor VIII and factor V and to function as an anticoagulant. Our results indicate that lactadherin competes efficiently with factor VIII and factor V for binding sites on synthetic phosphatidylserine-containing membranes with half-maximal displacement at lactadherin concentrations of 1 to 4 nM. Binding competition correlated to functional inhibition of factor VIIIa-factor IXa (factor Xase) enzyme complex. In contrast to annexin V, lactadherin was an efficient inhibitor of the prothrombinase and the factor Xase complexes regardless of the degree of membrane curvature and the phosphatidylserine content. Lactadherin also inhibited the factor VIIa-tissue factor complex efficiently whereas annexin V was less effective. Because the inhibitory concentration of lactadherin was proportional to the phospholipid concentration, and because lactadherin was not an efficient inhibitor in the absence of phospholipid, the major inhibitory effect of lactadherin relates to blocking phospholipid sites rather than forming inhibitory protein-protein complexes. Lactadherin was also an effective inhibitor of a modified whole blood prothrombin time assay in which clotting was initiated by dilute tissue factor; 60 nM lactadherin prolonged the prothrombin time 150% IntroductionLactadherin is a 47 000-Da molecular weight (MW) glycoprotein of milk-fat globules. It has also been known as PAS-6/7, indicating the 2 glycosylation variants, 1 bovine-associated mucoprotein, BA-46, P47, and MFG-E8. 2 Lactadherin has a domain structure of EGF1-EGF2-C1-C2 in which EGF indicates epidermal growth factor homology domains, and the C domains share homology with the discoidin family, including the lipid-binding C domains of blood coagulation factor VIII and factor V. 2 The second EGF domain displays an Arg-Gly-Asp motif, 3 which binds to the ␣ v ␤ 3 and ␣ v ␤ 5 integrins. 1,[4][5][6] The second C domain binds to phospholipids. 6 In milk-fat globules, lactadherin lines the surface of the phospholipid bilayer that surrounds the central triglyceride droplet, apparently stabilizing the bilayer. 7 Lactadherin decreases the symptoms of rotavirus infection in infants, possibly by binding to rotavirus particles via carbohydrate moieties. 8 In tissue sections, lactadherin is found localized on the apical portion of secretory epithelium in the breast. 7 Abundant expression by breast carcinoma tissue makes lactadherin a potential target for antigen-guided radiation therapy. 9 Lactadherin is also found on the apical surface of epithelia in the biliary tree, the pancreas, and sweat glands 7 and is synthesized by aortic medial smooth muscle cells. 10 Function in these tissues remains unknown. Lactadherin has been identified as a zona pellucida-binding protein on the a...

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Section: Introductionmentioning

confidence: 99%

Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites

Shi

Gilbert

2003

Blood

161

151

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“…Oligosaccharides promote the development of the bifid flora which, through a decrease in pH, impairs the multiplication of enterobacteria such as Shigella, Salmonella and E. coli, and inhibits the adhesion of bacteria such as Pneumococcus to mucosal surfaces, thus playing an important role in the prevention of infectious diseases in newborns 4 . Evidence indicates the existence of numerous other protective factors in addition to those described earlier, for example, gangliosides, resistance factor, interferon, fibronectin, glycosaminoglycans, and stimulated bile lipase 10,27,28 . In addition to its anti-infectious function, new studies have demonstrated that human milk can modulate the immune response in the nursing infant through immunomodulatory and anti-inflammatory substances that alter the host's reaction to injury 30 .…”

Section: Immunological Composition Of Human Milkmentioning

confidence: 77%

“…Some fat elements of human milk also show antimicrobial functions. Among the components of the cell membrane of fat droplets, glycoproteins such as mucins prevent the binding of bacteria and viruses to the intestinal mucosa 27,28 . In addition, the detergent action of free fatty acids and monoglycerides released by the hydrolysis of triglycerides mediates the lysis of bacteria, viruses and protozoans 27 .…”

Section: Immunological Composition Of Human Milkmentioning

confidence: 99%

Breastfeeding: making the difference in the development, health and nutrition of term and preterm newborns

Nascimento

Issler

2003

Rev. Hosp. Clin.

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Breastfeeding is the natural and safe way of feeding small infants, providing nutritional, immunological, psychological and economic recognized and unquestionable advantages. These qualities are especially important in premature infants, because of their vulnerability. Despite highly desirable, there is, in general, little success in breastfeeding preterm infants, especially in special care neonatal units. There are evidences that a high supportive hospital environment, with an interdisciplinary team, makes possible to these infants to be breastfed. In this article, the authors present an up-to-date review about the components of human milk and its unique characteristics, as well as describes aspects that make the breast milk particularly suitable for feeding the premature newborn. DESCRIPTORS: Infant feeding. Breastfeeding. Human milk. Newborn. Premature infant.

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“…One of the isolated proteins of bovine MFGM, namely fatty acid binding protein (FABP), has been found to inhibit the growth of some breast cancer cell lines in vitro at extremely low concentrations [Kromminga et al, 1990;Peterson et al, 1998b;Spitsberg & Gorewit, 2002;Spitsberg et al, 1995]. Furthermore, they demonstrated the presence of the onco-suppressor BRCA1 protein in bovine and human MFGM [Spitsberg & Gorewit, 1998].…”

Section: Phospholipidsmentioning

confidence: 99%

Composition, Properties and Nutritional Aspects of Milk Fat Globule Membrane – A Review

El-Loly¹

2011

Pol. J. Food Nutr. Sci.

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processes and defense mechanisms in the newborn [Cavaletto et al., 2006].The stabilizing membrane acts as reactive sorts on the interface between the barriers of milk serum. As such, it can be globule and rate-controlling for a host of physical and of enzymes chemical interactions, e.g., binding mace elements; controlled release of the polar materials products of lipolysis; transfer of milk serum; maintenance of emulsion into stability by prevention of globule fusion; availability of fatty acids and cholesterol for micellar absorption in the small intestine; and destabilization by creaming, clumping, churning, freeze-thaw, and heating, resulting in loosely bound substances into milk transfer serum. Worthy of notice is that the interactions are dynamic.Moreover, it is assumed that the MFGM proteins also possess specific nutritional properties. As such, due to their origin, composition and structure, MFGM polar lipids and proteins could be used as an emulsifier or stabilizer, combining technological and nutritional functionality [Mulder & Walstra, 1974;Anderson & Cawston, 1975;Patton & Keenan, 1975;Patton & Jensen, 1975, 1976Keenan et al., 1983;Mather & Keenan, 1983; McPherson & Kitchen, 1983; Walstra & Jenness, 1984;Keenan & Dylewski, 1985 Bucbheim, 1986;Mather, 1987; Keenan et al., 1988;Keenan & Dylewski, 1995;Keenan & Patton, 1995;Mather & Keenan, 1998;Danthine et al., 2000; Keenan, 2001; Keenan & Mather, 2002; Ollivier--Bousquet, 2002;Lopez et al., 2006Lopez et al., , 2007Sanchez-Juanes et al., 2009;Zamora et al., 2009]. Composition, Properties and Nutritional Aspects of Milk Fat Globule Membrane -a Review Mohamed Mansour El-Loly Dairy Department, National Research Centre, Dokki, Cairo, EgyptKey words: milk fat globule membrane, mammary gland, isolation, structure, stability, nutritional, nutraceuticalIn the last few years, knowledge on the composition and properties of the milk fat globule membrane (MFGM) increased significantly. It is now recognized that the MFGM is highly complex in structure and composed of different protein and lipid components with specific technological and nutritional properties. As such, MFGM materials have been isolated and characterized as valuable ingredients for incorporation into new food products. However, MFGM are also sensitive to modification during isolation and processing, and care should be taken to standardize the composition and characteristics of the membrane to maintain its unique properties during application in food products.The MFGM is subject to changes in composition and structure from the moment the fat globule leaves the mammary secretory cell. Upon milk harvesting and further milk handling, further changes to the MFGM take place. Depending on the type and degree of treatment, this may involve different physico-chemical interactions between various membrane components, the loss of membrane components and/or adsorption of components from the milk plasma. However, the effects appear to be variable and dependent on physiological (animal) factors, and much remains ...

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Glycoproteins of the Human Milk Fat Globule in the Protection of the Breast-Fed Infant against Infections

Cited by 138 publications

References 48 publications

Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites

Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites

Breastfeeding: making the difference in the development, health and nutrition of term and preterm newborns

Composition, Properties and Nutritional Aspects of Milk Fat Globule Membrane – A Review

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