Variation in the Biochemical Forms of Transforming Growth Factor-α Present in Human Milk and Secreted by Human Milk Macrophages

Wagner, Carol L.; Forsythe, Donna W.; Pittard, William B.

doi:10.1159/000244253

Cited by 18 publications

(22 citation statements)

References 21 publications

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“…The absence of these higher molecular mass isoforms from later postnatal age AM media samples, the minimal staining of rainbow molecular mass markers, and negative secondary control support the premise that these isofoms are true TGFa-like moieties reacting with the TGFa MAb. Similar higher molecular mass TGFa isoforms have been identified in the medium of human milk macrophages in our laboratory with only the 6-kD isoform identified in human milk supernatant (42). It appears, therefore, that higher molecular mass isoforms >22 kD are secreted by AM and may represent aggregation at disulfide bonds, or as yet, another unidentified member of the EGF family with structural homology to TGFa.…”

Section: Discussionsupporting

confidence: 78%

Secretion of Transforming Growth Factor-α (TGFα) by Postnatal Rabbit Alveolar Macrophages

et al. 1995

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Section: Discussionsupporting

confidence: 78%

Secretion of Transforming Growth Factor-α (TGFα) by Postnatal Rabbit Alveolar Macrophages

et al. 1995

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“…Okada et al (18) verified TGF-␣ concentration in human milk using a specific RIA assay. Wagner et al (29) have found that human milk contains different biochemical forms of TGF-␣ that can originate from human milk macrophage secretion. Results from these studies have shown that TGF-␣ concentration in mature milk is markedly lower compared with EGF levels.…”

Section: Discussionmentioning

confidence: 99%

Increased Epidermal Growth Factor Levels in Human Milk of Mothers with Extremely Premature Infants

et al. 2003

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Maternal milk is the major source of nutrients and growthpromoting substances in the first weeks of life for the majority of neonates. Epidermal growth factor (EGF) and transforming growth factor-␣ (TGF-␣) are trophic peptides present in human milk with significant healing effects on injured gastrointestinal mucosa. Decreasing gestational age of neonates is associated with higher risk of developing gastrointestinal disorders, and human milk provides better protection against these diseases compared with formula. The aim of this study was to evaluate the concentrations of EGF and TGF-␣ in human milk collected from mothers with infants born: extremely preterm, preterm, and full term. Milk samples were collected at the end of first, second, and fourth week postpartum from each mother of infants born in one of the three gestational age groups: extremely preterm (23-27 wk, n ϭ 16), preterm (32-36 wk, n ϭ 16), and full term (38 -42 wk, n ϭ 15). Milk concentrations of EGF and TGF-␣ were quantified with a homologous RIA in the milk aqueous fraction. Concentrations of EGF in human milk from the extremely preterm group (23-27 wk) were significantly higher compared with values from the preterm and full-term groups throughout the first month of lactation. A similar pattern was observed with human milk TGF-␣; however, milk TGF-␣ levels were lower than EGF.In conclusion, we have found higher concentrations of EGF and TGF-␣ in human milk of mothers with extremely preterm babies. These data may indicate the potential importance of milk-borne EGF and TGF-␣ for the development of extremely premature infants. (Pediatr Res 54: 15-19, 2003) Abbreviations EGF, epidermal growth factor EGF-R, epidermal growth factor receptor EPT, extremely preterm FT, full term PT, preterm NEC, necrotizing enterocolitis TGF-␣, transforming growth factor-␣ Human milk is a unique and well-balanced source of nutrition for the newborn. Milk contains not only major nutrients (proteins, carbohydrates, and lipids) but also a variety of components such as minerals, vitamins, enzymes, hormones, growth factors, and immunoglobulins important for growth and healthy development during the neonatal period (1-3). As advances in neonatal care have significantly increased, the survival of extremely prematurely born neonates have increased (4). Yet these infants have the highest incidence of morbid events, such as NEC (5). Questions have arisen about the most suitable and relevant nutritional support for these immature infants (6, 7).Within the last three decades, a large number of biologically active peptides have been identified in human milk (8 -10), and the list is continuously growing (11-13). Among these, EGF is one of the major peptide growth factors present both in colostrum and human milk (14 -17). Human milk EGF levels are highest in the first days after parturition and then gradually decrease during the first 2 wk of lactation (17). Another structural homolog of EGF, TGF-␣ is also present in human colostrum and milk (15, 18), but at much lower concentrations ...

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“…Human milk samples were placed in 4°C then processed within 8 h of expression. Milk was spun at 1,000 g for 25 min at 4°C to achieve separation of the cellular, fat and aqueous compartments of human milk as previously described [26]. Following separation, the AHM samples were frozen at -20°C until further testing.…”

Section: Methodsmentioning

confidence: 99%

“…Macrophages were isolated from whole human milk according to the methods previously reported [26]. Isolated macrophages were placed in culture at a concentration of 1 !…”

Section: Methodsmentioning

confidence: 99%

“…Milk leukocytes, particulary macrophages that are the predominant cell type in mature human milk, also have been shown to secrete growth factors, including TGF· [26]. While these cells are thought to play a role in the regulation of GI tract development as well as its evolving immunologic function [32,33], there is little known about how these cells may exert their influence on gut epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Recombinant TGFα, Human Milk, and Human Milk Macrophage Media on Gut Epithelial Proliferation Is Decreased in the Presence of a Neutralizing TGFα Antibody

1998

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Objective: An in vitro model was devised to compare the relative effects of recombinant transforming growth factor-alpha (TGFα), aqueous human milk, and human milk macrophage (HMM) medium on human fetal small intestinal cell (FHs-74) proliferation. Methods: Recombinant TGFα at increasing concentrations (range 0.01–1,000 ng/ml media), the aqueous fraction of human milk (AHM), or HMM medium was added to FHs-74 cells in the presence or absence of a neutralizing TGFα antibody (1 µg/ml medium). At 24 h, cell proliferation was measured and expressed as percent control. The experimental variables were (1) activators of cell growth (TGFα, AHM, and HMM medium); (2) increasing concentrations of TGFα, and (3) neutralizing antibody to TGFα. The dependent variable for all experiments was cell proliferation. Results: Significant effects for growth stimulators and TGFα concentration as measured by cell proliferation were found. Specifically, there was a dose-dependent effect of TGFα on cell proliferation to the 5-ng/ml concentration, with a plateau reached in cell proliferation at higher concentrations. The stimulatory effect of TGFα was decreased in the presence of TGFα antibody (mean ± SD 22 ± 7.1% decline, p < 0.001). In the presence of TGFα antibody, there was a 25 ± 3.1% decline in HM-stimulated growth (p < 0.004), and a 27.6 ± 3.2% decline in HMM medium-stimulated growth (p < 0.001). Conclusions: Neutralization of recombinant TGFα and that present in human milk and HMM medium by TGFα antibody led to a consistent decrease in in vitro human fetal small intestine epithelial proliferation without affecting cell viability. These results support the hypothesis that TGFα, whether derived from human recombinant sources, human milk or HMM medium has a measurable, trophic effect on in vitro human gut epithelial cells.

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Variation in the Biochemical Forms of Transforming Growth Factor-α Present in Human Milk and Secreted by Human Milk Macrophages

Cited by 18 publications

References 21 publications

Secretion of Transforming Growth Factor-α (TGFα) by Postnatal Rabbit Alveolar Macrophages

Secretion of Transforming Growth Factor-α (TGFα) by Postnatal Rabbit Alveolar Macrophages

Increased Epidermal Growth Factor Levels in Human Milk of Mothers with Extremely Premature Infants

The Effect of Recombinant TGFα, Human Milk, and Human Milk Macrophage Media on Gut Epithelial Proliferation Is Decreased in the Presence of a Neutralizing TGFα Antibody

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