Feto-maternal interactions and immunological tolerance of the mother to her semiallogeneic fetus

Pregnancy is a cooperative interaction between the mother and her fetus, allowing survival and normal growth of the fetus. Successful pregnancy remains a fascinating phenomenon as it resists the immunological rules of rejection. Immunological recognition of the fetus is vital for maintenance of gestation. The maternal immune system undergoes changes that lead to tolerance of the fetus. Inadequate recognition of fetal antigens may cause abortion. In fact, fetal cells express paternal alloantigens that are not recognized as foreign by the mother. A special balance between lymphocytes is present at the feto-maternal interface to control the immune response. In addition, placenta! trophoblasts act as a physical barrier and exert an immunoregulatory function. Trophoblast cells regulate the expression of human leucocyte antigens. Dysfunction of these cells leads to morphological and functional alterations of the feto-maternal barrier as well as to recurrent spontaneous abortions. Uterine natural killer cells are appropriate residents of the materno-fetal interface to support the adaptation of the blood vessels of the pregnant uterus and regulate trophoblast invasion into the decidua and myometrium. Cytokines are involved at the feto-placental unit by adapting normal T-cell trafficking and modulating the inflammatory process. This study discusses the complex immunological aspects of immune tolerance and the balance of immunity in pregnancy in terms of the role of the human leucocyte antigen, placental trophoblasts, maternal immunosuppression, immune cells, cytokines and immunoregulatory molecules at the feto-maternal interface

Histological study on the effect of sodium azide on the corpus striatum of albino rats and the possible protective role of L-carnitine

Sodium azide is a white crystalline powder used as a broad-spectrum biocide in agriculture and as a preservative in aqueous laboratory reagents. The aim of this study was to determine the effect of sodium azide on the corpus striatum and the possible protection by L-carnitine. Twenty-four adult male albino rats, weighing 150-200 g, were used in this study. The animals were divided equally into four groups. Group I was the control group. Group II received sodium azide at a dose of 20 mg/kg/day orally for 60 consecutive days. Group III received sodium azide at the same previous dose in addition to L-carnitine at a dose of 100 mg/kg/day intraperitoneally for 60 consecutive days. Group IV received only L-carnitine at the same previous dose once daily for 60 consecutive days. At the end of the experiment, all the animals were anesthetized, the brain was dissected out and the regions of the corpus striatum were subjected to light and electron microscopic examination. Moreover, the number of degenerated nerve cells was counted and the results were analyzed statistically. By light and electron microscope, the nerve cells [pyramidal cells and granular cells] of group II animals showed degenerative changes in the form of shrunken darkly stained and hyperchromatic nuclei. Some apoptotic cells were observed. There were multinucleated giant cells in some areas and small vacuoles in the neuropil. Also, cytoplasmic vacuolations and swollen mitochondria with indistinct cristea were detected. The neuropil in some areas contained extravasation of blood elements. The nerve fibers showed fragmentation, thickening, aggregation, and defective myelination. Statistically, there was a highly significant increase in the mean number of degenerated neurons. In group III, L-carnitine preserved most of the histological and ultrastructural profile of the corpus striatum [nerve cells and nerve fibers], with a significant decrease in the rate of neuronal loss. The results of the current study showed that the administration of L-carnitine might protect against neurotoxicity produced by exposure to sodium azide

Role of 5-azacytidine in the differentiation of rat bone marrow mesenchymal stem cells into cardiomyogenic cells

Increasing attention is being paid to the use of mesenchymal stem cells [MSCs] for treatment of human diseases such as myocardial infarction. To study the differentiation of the bone marrow mesenchymal stem cells [BM-MSCs] into cardiomyogenic cells using 5-azacytidine. Forty adult male albino rats were used in this study. BM-MSCs were isolated and cultured in a complete Dulbecco's modified Eagle's medium containing 1% antibiotics and 10% fetal bovine serum [the control group]. Second passaged cells were treated with 10micro moI/I 5-azacytidine for 72h. Then, the medium was removed and kept in a 5-azacytidine-free medium for 4 weeks [the 5-azacytidine-treated group]. The adherent cells of both groups were examined using a phase-contrast microscope and a transmission electron microscope. Expressions of cytoskeleton protein desmin and cardiac muscle-specific cardiac troponin T were assessed by immunohistochemistry. BM-MSCs of the control group were spindled and star shaped with multiple processes and vesicular nuclei. After adding 5-azacytidine for 1 week, the cells showed multinucleation. On the second week, the cells formed stick-like structures. The cells showed extensive cytoplasmic striations in the third week. Finally, in the fourth week, the cells formed myotube-like structures. Immunohistochemical staining of cells of the 5-azacytidine-treated group revealed a positive immune reaction for desmin and cardiac troponin-T. Ultrastructural examination of the 5-azacytidine-treated group revealed that the cells were elongated with central oval large nuclei. The mitochondria were elongated with well developed cristae. There were abundant free ribosomes and extensive dilated rough endoplasmic reticulum. Myofibrils started to appear in the peripheral part of the cytoplasm and T-tubules appeared. MSCs can be differentiated in vitro by 5-azacytidine into cardiomyogenic cells, which are important for repairing infracted myocardium

Effect of glucocorticoids on surface IL-10 receptors and intracellular IL-10 in mouse splenocytes, thymocytes, monocytes, and dendritic cells: immunofluorescence, confocal microscopy, and electrophoresis study

Glucocorticoids are capable of stimulating the secretion of interleukin -10 [IL-10] by leukocytes. The probable role of glucocorticoids in the susceptibility of immune cells to IL-10 mediated actions has not yet been studied. In this study, we examine the expression of IL-10 and IL-10 receptors [IL-1OR] in mouse splenocytes, thymocytes, monocytes, and dendritic cells. In addition, we determined the effects of the glucocorticoid [methylprednisolone] on IL-10 secretion and IL-10R expression in the previous immune cells. Forty-eight male mice with the C57BL/6 genetic background were used. The animals were 10-12 weeks of age and were divided equally into two groups. The animals in group I were provided with a balanced standard diet and water ad libitum. The animals in group II were provided with a balanced standard diet and methylprednisolone [o.5mg/kg/day] in the drinking water daily for 7 days. The mice in groups I and II were sacrificed after 7 days and the spleen and thymun were removed to isolate the splenocytes and thymocytes. The blood was also aspirated to isolate monocytes. Group III included mice with the mouse dendritic cell line [JAWS II]. Cells of the mice in this group were divided into two subgroups. Group IIIa included the dendritic cells cultured in Iscove's modified Dulbecco's medium and group IIIb included the dendritic cells cultured in Iscove's modified Dulbecco's medium supplemented with methylprednisolone [2micro g/ml] for 6h. All the previous cells were processed for immunohistochemistry, western blotting, immunoassay analysis, and electrophoresis. All the cells examined showed an intense fluorescent surface expression of IL-10R as detected by the immunofluorescence technique. On using methylprednisolone, there were few and faint expressions of IL-1OR. The intracellular IL-10 molecules were few in the dendritic cells but after treatment with methylprednisolone, the IL-10 molecules were numerous and intense. Western blotting and electrophoresis techniques showed intense precipitation of IL-10 at 35 kDa and faint precipitation of IL-10R at 110kDa in all the cells examined after glucocorticoid treatment. There was also a highly significant [P<0.001] increase in the level of IL-10 in all the cells examined after using methylprednisolone as detected by immunoassay. Our findings could contribute toward understanding the immunomodulating mechanism of the action of glucocorticoids, which may result in greater therapeutic benefit in some diseases by enhancing the synthesis of the anti-inflammatory cytokine IL-10 and decreasing the expression of IL-1OR in some immune cells