In the cow, maternal immunity is exclusively mediated by colostral Igs, but the receptor responsible for the IgG transport has not yet been identified. The role of an IgG-Fc receptor (FcRn) that resembles a class I MHC Ag in transporting IgGs through epithelial cells was recently shown in selected species. We now report the cloning and characterization of the bovine FcRn (bFcRn). The cDNA and deduced amino acid sequences show high similarity to the FcRn in other species, and it consists of three extracellular domains, a hydrophobic transmembrane region, and a cytoplasmic tail. Despite the high similarity of the extracellular domains with other species, the bovine cytoplasmic tail is the shortest thus far analyzed. Aligning the known FcRn sequences, we noted that the bovine protein shows a 3-aa deletion compared to the rat and mouse sequences in the α1 loop. Furthermore, we found a shorter transcript of the bFcRn reflecting an exon 6-deleted mRNA, which results from an inadequate splice acceptor site in intron 5 and produces a transmembrane-deficient molecule, as was previously demonstrated in the related MHC class I gene family in mouse and humans. The presence of bFcRn transcripts in multiple tissues, including the mammary gland, suggests their involvement both in IgG catabolism and transcytosis.
SUMMARYMaternal immunity is mediated exclusively by colostral immunoglobulins in ruminants. As the neonatal Fc receptor (FcRn) is suggested to be involved in the transport of immunoglobulin G (IgG) in the mammary gland, we cloned this receptor from sheep and analysed its expression in the mammary gland around the time of parturition and also in the small intestine from the newborn lamb. FcRn heavy-chain mRNA was detected (by using in situ hybridization) exclusively in the acinar and ductal epithelial cells in mammary gland biopsies both before and after parturition. Immunohistochemistry revealed that the cytoplasm of the epithelial cells of the acini and ducts in the mammary gland biopsies stained homogeneously before parturition. A remarkable difference was observed in the pattern after lambing, where the apical side of the cells was strongly stained. The presence of the FcRn in the acinar and ductal epithelial cells of the mammary gland, and the obvious change in distribution before and after parturition, indicate that the FcRn plays an important role in the transport of IgG during colostrum formation in ruminants. Immunohistochemical analysis detected a strong apical and a weak basal FcRn signal in the duodenal crypt cells of a neonatal lamb, which have been previously demonstrated to secrete IgG1 in newborn ruminants. The FcRn was not detected in the duodenal enterocytes, which absorb intact IgG from the colostrum in a non-specific manner. These data suggest that FcRn is involved in IgG1 secretion in ruminant epithelial cells.
In ruminants, protective immunoglobulins are transferred to the newborn via colostrum to mediate maternal immunity. There is a high selectivity in the transport of immunoglobulins from the maternal plasma across the mammary barrier into the colostrum, and only IgG1 is transferred in large amounts. We have recently analysed the expression of the neonatal Fc receptor (FcRn) in sheep mammary gland around parturition. Re-analysing this issue in bovine confirmed our previous data indicating that FcRn is homogeneously localized in the mammary gland acinar cells before parturition, however a remarkable difference was observed in the pattern after calving, where only the apical side of the cells was strongly stained. The presence of the FcRn in the acinar epithelial cells of the mammary gland and the obvious change in distribution before and after parturition indicate that FcRn plays an important role in the IgG transport during colostrum formation in ruminants.
Morphofunctional changes in hypothalamic neurons are highly energy dependent and rely on mitochondrial metabolism. Therefore, mitochondrial adenosine triphosphate production plays a permissive role in hypothalamic regulatory events. Here, we demonstrated that in the female rat hypothalamus, mitochondrial metabolism and tissue oxygenation show an asymmetric lateralization during the estrous cycle. This asymmetry was not detected in males. The observed sidedness suggests that estrous cycle-linked hypothalamic functions in females are based on hemispheric distinction. The novel concept of hypothalamic asymmetry necessitates the revision of hypothalamic neural circuits, synaptic reorganization, and the role of hypothalamic sides in the regulation of integrated homeostatic functions.
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