Lactation Stage-Related Expression of Sialylated and Fucosylated Glycotopes of Human Milk α-1-Acid Glycoprotein

Abstract

Background: Because terminal sugars of a-1-acid glycoprotein (AGP) are reported to be involved in antiinflammatory and immunomodulatory processes, their expressions might have an influence on the proper function of immune system of newborns. Here, relative amounts of sialylated and fucosylated glycotopes on human milk AGP over normal lactation were investigated. Materials and Methods: AGP concentration and relative amounts of its sialylated and fucosylated glycovariants were analyzed in early colostrum, colostrum, and transitional and mature milk samples of 127 healthy mothers by lectin-AGP enzyme-linked immunosorbent assay using a2,3-and a2,6-sialic acid and a1,2-, a1,3-, and a1,6-fucose specific biotinylated Maackia amurensis, Sambucus nigra, Ulex europaeus, Tetragonolobus purpureus, and Lens culinaris lectins, respectively. Results: AGP concentration in human milk was about 30 times lower than in plasma of lactating mothers and decreased gradually over lactation. Milk AGP showed significantly higher expression of sialylated and fucosylated glycotopes in comparison with those of plasma AGP. Milk AGP glycovariants containing a2,6-sialylated and a1,6-and a1,2-fucosylated glycotopes showed the highest relative amounts in early colostrums. With progression of lactation, the expressions of glycotopes a1,2-fucosylated decreased starting from Day 4 and those of a2,6-sialylated and a1,6-fucosylated from Day 8 of lactation, whereas the level of a2,3-sialyl-glycotope was almost constant over 45 days of lactation. In contrast, the expression of a1,3-linked fucose on AGP was low in colostrums and significantly higher in transitional and mature milk. Conclusions: The relative amounts of sialylated and fucosylated glycovariants of human hindmilk AGP significantly varied between Days 2 and 45 of normal lactation.

Terminal glycotope expression on milk fibronectin differs from plasma fibronectin and changes over lactation

“…Although according to Froehlich et al [21] there is no common pattern for glycosylation of milk glycoproteins over lactation, the sialylation and fucosylation changes are more or less similar to those of other milk glycoproteins, human milk oligosaccharides (HMOs), and those of the entire N-glycan repertoire of whey proteins from human milk [25]. The decrease of α2,6-sialylation (SNA-reactive) observed by us, with relatively stable α2,3-sialylation (MAA-reactive) over lactation, was found to be similar to that described recently for human milk AGP [26] and HMOs [27]. Also, the expression of sialylated and In Table 1 values are given as the mean ± SD and median and 25th-75th percentile in parentheses.…”

O-Glycosylation of α-1-Acid Glycoprotein of Human Milk Is Lactation Stage Related

“…Moreover, as suggested by Newburg, 2 some human milk oligosaccharides (HMOs) may provide a background for construction of innovative therapeutics as well as prophylactic bioagents given for neonates during the postnatal period, particularly those delivered preterm in unfavorable and detrimental conditions. So far the free HMOs, 1 human milk N-glycome, 5 and glycan profiles of N-and/or O-glycans of some glycoproteins, 6 such as lactoferrin, 7 bile salt-stimulated lipase, 8 secretory immunoglobulin A, 9,10 a-1-acid glycoprotein (AGP), 11 and fibronectin, 12 have been characterized in detail. Over the process of lactation, within milk maturation, the degree and type of sialylation and fucosylation of milk glycoproteins change and partly overlap with observed trends for HMOs abundantly present in milk.…”

“…Over the process of lactation, within milk maturation, the degree and type of sialylation and fucosylation of milk glycoproteins change and partly overlap with observed trends for HMOs abundantly present in milk. 6,11,12 Gao et al 13 have suggested that alteration in glycan structures during lactation goes hand in hand with a transformation in defense mechanisms that occur from newborns to young infants.…”

“…Additionally, its concentration decreased with milk maturation and correlates with the total protein concentration decline. 11 AGP glycosylation is tissue specific, is microheterogeneous in the degree of branching, fucosylation, and sialylation, and can change in relation to the physiopathological state of the human organism. 11,[23][24][25] Local-specific glycoforms of AGP have been reported for amniotic fluid 26 and human skim milk AGP, 11 and it was manifested by the increase of fucosylation as well as sialylation levels in comparison with those of normal as well as lactating mothers' plasma AGP.…”

“…Moreover, the degree of sialylation and fucosylation of milk AGP was strongly correlated with milk maturation. 11 The impact of the N-glycan part of plasma AGP on its function has been well documented. 23,24 The highly sialylated and fucosylated N-glycans of AGP are known to possess anti-inflammatory properties and to participate in the modulation of leukocyte-endothelial interactions by binding to E-or P-selectin.…”