Honorio-França AC, Carvalho MPSM, Isaac L, Trabulsi LR, Carneiro-Sampaio MMS. Colostral Mononuclear Phagocytes are Able to Kill Enteropathogenic Escherichia coli Opsonized with Colostral IgA. Scand J Immunol 1997;46:59-66 Enteropathogenic Escherichia coli (EPEC) is the main aetiological agent of acute diarrhoea among low socioeconomic level infants in developing countries. Breast-feeding provides infant protection against acute gastrointestinal and respiratory infections; however, little is known about the protective role of colostral phagocytes in the gut of newborn infants. In the present investigation we studied the ability of human colostral MN phagocytes to kill EPEC as well as the interactions between these cells and colostral and serum opsonins. The authors observed that the microbicidal activity of colostrum MN phagocytes was dependent on previous EPEC opsonization with colostral supernatant or blood serum. A defatted colostrum supernatant pool presented opsonic activity for EPEC killing at levels equivalent to those of normal serum. IgA-depleted colostrum supernatant showed significantly lower opsonic activity, whereas purified IgA from the same colostrum pool was a potent opsonin which induced EPEC killing at levels equivalent to those of untreated colostrum. Colostral MN phagocytes are able to release superoxide anion when incubated with both EPEC opsonized with untreated colostrum and purified IgA. Purified IgA was also able to restore opsonic activity of IgA-depleted colostrum. A colostrum pool without C3 and IgG induced EPEC killing by colostral MN phagocytes at rates equivalent to those of untreated colostrum supernatant. Addition of an IgM MoAb (My43) anti-human Fca receptor resulted in a significant inhibition of EPEC killing when bacteria were opsonized with purified IgA, suggesting an interaction between IgA and FcaR. With respect to serum opsonins, we observed that IgG plus complement component C3 were necessary to induce EPEC killing by the colostrum MN phagocytes. Colostral phagocyte killing of enteropathogenic bacteria may represent an additional mechanism of breast-feeding protein against intestinal infections during the first week of life.

These results suggest that the ability of phagocytes to eliminate ETEC depends on the activation of cellular oxidative metabolism; moreover, activation of colostral phagocytes is likely an additional breast-feeding protection mechanism against intestinal infections in infants.

BackgroundObesity in pregnancy is associated with systemic inflammation, immunological changes and adverse maternal-fetal outcomes. Information on the association between maternal obesity and breast milk composition is scarce. This study describes changes and relationships between biochemical and immunological parameters of colostrum and serum of overweight and obese women.MethodsColostrum and blood samples were collected from 25 normal weight, 24 overweight and 19 obese women for determination of glucose, total protein, triglycerides, cholesterol, immunoglobulins, complement proteins (C3 and C4), fat and calorie content and C-reactive protein (CRP).ResultsGlucose was higher in colostrum of obese women (p = .002). In normal weight and obese women, total protein content was higher in colostrum than in serum (p = .001). Serum triglycerides (p = .008) and cholesterol (p = .010) concentrations were significantly higher in overweight and obese women than in their normal weight counterparts, but in colostrum their concentrations were similar across the three groups. Secretory IgA (sIgA) in colostrum and IgA in serum concentrations were significantly higher (p = .001) in overweight and obese mothers, whereas IgG and IgM concentrations did not vary among the groups (p = .825). Serum C3 (p = .001) and C4 (p = .040) concentrations were higher in obese women. No differences in colostrum complement proteins were detected among the groups. Calorie content (p = .003) and fat (p = .005) concentrations in colostrum and serum CRP (p = .002) were higher in obese women.ConclusionsThe results corroborate the hypothesis that colostrum of overweight and obese women undergoes biochemical and immunological changes that affect its composition, namely increasing glucose concentrations, calorie content, fat and sIgA concentrations.

Some studies report that hormone melatonin can be found in human milk, but the daily variation in colostrummelatonin is not available. This study verified the effects of milk collection time (diurnal/nocturnal) on colostralmelatonin levels and the ability of this hormone to modulate colostral phagocyte activity. Colostrum sampleswere collected from 30 mothers during the day and night, for a total of 60 samples. We determined melatoninlevels in colostrum and superoxide release and bacterial killing by colostral phagocytes. Melatonin levelswere higher in colostrum samples collected at night. Phagocytes in nocturnal colostrum samples increasedspontaneous superoxide release. In diurnal colostrum samples, mononuclear (MN) phagocytes increasedsuperoxide release when exposed to enteropathogenic Escherichia coli (EPEC), but not polymorphonuclear(PMN) phagocytes. Phagocytes exposed to both EPEC and melatonin had higher superoxide release,independent of phagocyte type and colostrum collection period. Phagocytosis rate was higher in colostrumsamples collected at night. In diurnal samples, EPEC killing by MN phagocytes was lower than by PMNphagocytes. Phagocytosis increased significantly in the presence of melatonin in both MN and PMN cells,irrespective of colostrum collection period. In response to melatonin, MN phagocytes from both diurnaland nocturnal samples increased bactericidal activity, whereas colostral PMN phagocytes increased it onlyin diurnal samples. The melatonin increased in the intracellular Ca2+ levels. The highest intracellular Ca2+release were found in MN phagocytes diurnal samples. These results confirm that melatonin levels in humancolostrum follow a day-night variation and increase phagocytic activity of colostral cells against bacteria

Our results support the hypothesis that the colostrum of diabetic mothers suffers biochemical and immunological alterations that affect the levels of its components.

The effects of secretory immunoglobulin A (SIgA) interaction with its specific Fcα receptors on colostral phagocytes needs further investigation, especially with respect to diabetic women. Accordingly, we studied the colostrum of hyperglycemic women to assess SIgA interactions with Fcα receptors of macrophages as well as the functional activity of these cells. The women were divided for colostrum sampling according to their glycemic status: normoglycemia (N = 51), mild hyperglycemia (N = 23), and diabetes (N = 25) groups. We determined the FcαR expression, the IgA on the surface and the surface-bound IgA in colostrum macrophages. We also evaluated the superoxide release and bactericidal killing of these cells. Colostral phagocytes expressed FcαR, contained IgA on the surface and are able to bind to purified SIgA. The bactericidal activity of colostral phagocytes from the hyperglycemic women was similar to that of normoglycemic only when SIgA was used as opsonin. Addition of a MoAb anti-human Fcα receptor resulted in a significant decrease of superoxide release and bacterial killing by macrophages when bacteria were opsonized with purified SIgA, suggesting an interaction between SIgA and FcαR. The stimulatory effects of SIgA on the functional activity of phagocytes therefore protect infants, especially of diabetic women, against intestinal infections.

Breast milk contains bioactive components that contribute to newborn development. However, colostrum may undergo biochemical and immunological changes as a function of maternal overweight and obesity. To investigate this hypothesis, this study determined the levels of hormones and immunological markers in the serum and colostrum of overweight and obese mothers. Colostrum and serum samples were collected from 15 normoweight, 15 overweight, and 15 obese women for determination of leptin, adiponectin, cytokines (TNF-α, IL-6, IL-10), and C-reactive protein (CRP). Obese mothers exhibited higher levels of serum TNF-α, IL-6, and CRP, serum and colostrum leptin and colostrum adiponectin and lower levels of serum adiponectin. Leptin levels in maternal serum and colostrum were positively correlated, as was pre-pregnancy BMI and serum TNF-α, IL-6, CRP, and leptin. Adiponectin levels in colostrum and serum were negatively correlated. The results suggest that obesity changes hormonal and immunological components of maternal serum and colostrum. The modifications can have short-term and long-term effects on newborn development. © 2016 BioFactors, 43(2):243-250, 2017.

Malaria is a major infectious disease in several countries and is caused by protozoa of the genus Plasmodium. In vivax malaria patients, inflammatory processes occur, as well as changes in cytokines and blood flow. The present study analyzed the cytokine modulation of blood viscosity from patients infected with Plasmodium vivax (P. vivax). Blood samples were collected from 42 non-infected individuals (control group) and 37 individuals infected with P. vivax. The IL-2, IL-4, IL-6, IL-10, TNFα, TGF-β and IL-17 cytokine concentrations in the serum were assessed, and the blood rheological properties were determined. The analysis of blood viscosity for shear rates revealed that the blood viscosity of the infected patients was significantly greater than that of the non-infected individuals. The viscosity of the blood was greater in the infected individuals than in the non-infected subjects. The serum from individuals with P. vivax infections exhibited higher IFN-γ and IL-17 concentrations and lower TGF-β levels. Incubation of the blood from infected individuals with IL-17 or IL-17 associated with IFN-γ reduced the viscosity to rates equivalent to the blood from non-infected individuals. Independently of cytokine modulation, no correlation was found between the parasitemia and blood viscosity of the infected patients. These data suggest that the alterations of blood viscosity are relevant as an auxiliary tool for the clinical diagnosis of disease. In malaria, erythrocytes are more sensitive to osmotic shock, and the reduction of viscosity by IL-17 may be related to a possible immunomodulator agent during infection.