Granulocyte Colony-Stimulating Factor Is Present in Human Milk and Its Receptor Is Present in Human Fetal Intestine

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Abstract
Objective. Human milk provides neonates with a meaningful degree of protection from infection, but the responsible mechanisms are not well understood. Discovering these mechanisms is important, because of the possibility of supplementing infant formulas with factors that simulate human milk9s protective capacity. We postulated that granulocyte colony-stimulating factor (G-CSF), a cytokine known to augment antibacterial defenses through its salutory effect on neutrophil production, might be one such factor. To test this hypothesis, we quantified G-CSF in milk of healthy women and those with intraamniotic infection, and sought the presence of functional G-CSF receptors (G-CSF-R) in fetal/neonatal intestinal villi. Study Design. G-CSF was measured by enzyme-linked immunoassay in 126 milk samples obtained from breast-feeding women, and the concentrations were analyzed according to gestational age, postpartum day of collection (first 2 days vs greater 2 days), and the presence versus absence of intraamniotic infection. G-CSF-R messenger ribonucleic acid transcripts were sought from fetal/neonatal intestine using reverse transcriptase polymerase chain reaction, and localized using in situ RT-PCR. G-CSF-R protein, and specific intracellular signaling proteins (Janus tyrosine kinase-1, Janus tyrosine kinase-2, and tyrosine kinase-2), were sought by immunohistochemistry. Results. All milk samples contained G-CSF, and significantly more G-CSF was contained in milk collected during the first 2 postpartum days than during subsequent days. Milk from women who delivered prematurely had less G-CSF during the first 2 postpartum days than milk from women who delivered at term. When intraamniotic infection was present, the concentration of G-CSF in milk was elevated significantly compared with concentrations in milk of noninfected women. G-CSF concentrations were also higher in milk collected during the first 2 postpartum days from women who had received intrapartum recombinant G-CSF treatment, compared with milk obtained from women with intraamniotic infection, regardless if they delivered prematurely or at term. G-CSF-R messenger ribonucleic acid and protein were expressed on fetal villus enterocytes, and Janus tyrosine kinase-1, Janus tyrosine kinase-2, and tyrosine kinase-2 were present within the cytoplasm of these cells. Conclusions. Human milk contains substantial quantities of G-CSF. G-CSF-R are abundant on villus enterocytes, and specific proteins associated with G-CSF-R signaling are present in these cells.