ABSTRACT
It has been proposed that progesterone (P4) induces the suppression of immune responses, particularly during pregnancy. However, knowledge about the mechanisms involved has remained largely elusive. We demonstrate herein that peripheral blood NK (PBNK) cells express both classical progesterone receptor (PR) isoforms and are specifically affected by the actions of P4 through two apparently independent mechanisms. Progesterone induces caspase-dependent PBNK cell death, which is reversed by two different anti-progestins, ZK 98.299 and RU 486, supporting the involvement of classical PR isoforms. It was suggested that CD56(bright)CD16(-) killer Ig-like receptor (KIR)(-) NK cells might represent precursor cells, which, upon activation, acquire the features of a more mature NK subset expressing KIR receptors. The present study demonstrates that PR expression seems to be restricted to more mature KIR(+) PBNK cells. The expression of PR had a functional counterpart in the suppressive effect of P4 on IL-12-induced IFN-gamma secretion. This cytokine suppression was mainly observed in KIR(+) PBNK cells, without affecting the high secretion of IFN-gamma by CD56(bright) PBNK cells. The lack of PR expression on CD56(bright)KIR(-) PBNK cells provides an additional phenotypic marker to test the idea that they might represent the PBNK precursors selectively recruited into the endometrium where they differentiate to become the uterine NK cells. Additionally, these findings may be relevant to NK cell function in viral immunity, human reproduction, and tumor immunity.
Subject(s)
Apoptosis , Killer Cells, Natural/metabolism , Lymphocyte Subsets/metabolism , Progesterone/metabolism , Receptors, Progesterone/metabolism , Adult , Female , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-12/immunology , Interleukin-12/metabolism , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/immunology , Male , Mifepristone/pharmacology , Signal TransductionABSTRACT
Oxidative stress and reticulocyte maturity index (RMI) were studied in 27 patients who underwent bone marrow transplantation (BMT). Plasmatic lipoperoxide levels of those patients with unfavorable evolution were significantly increased on days 12-14 post-transplant (median 1.83 microM, range 0.78-5.82) compared with preconditioning levels (median 1.05 microM, range 0.36-1.84) (p < 0.05). Patients with favorable evolution revealed significantly higher lipoperoxide levels during conditioning regime (median 1.42 microM, range 0.31-4.50) (p < 0.05). Starting from the 3rd post-transplant week a significant and continuous decrease was observed, with a median of 0.77 microM (range 0.21-1.48 p < 0.05) for the 3rd, and a median of 0.60 microM (range 0.11-1.48 for the 4th week (p < 0.01). A significant increase in total antioxidant activity was observed in the three patients who died up to the 35 days post-transplant. Recovery of bone marrow function was detected by RMI after a median time of 17 days (range 11-24) post-allogeneic transplantation. The threshold established for absolute neutrophil count was achieved after a median of 21 days (range 14-28) (p < 0.001). An increase of plasma lipoperoxides on days 12-14 post-transplant may be a predictive value of unfavourable evolution. RMI was the earlier indicator of engraftment in allogeneic BMT.
Subject(s)
Bone Marrow Transplantation , Bone Marrow/physiology , Oxidative Stress , Whole-Body Irradiation , Adolescent , Adult , Analysis of Variance , Bone Marrow/metabolism , Bone Marrow/radiation effects , Bone Marrow Cells , Child , Female , Humans , Lipid Peroxides/blood , Lipid Peroxides/metabolism , Male , Middle Aged , Neutrophils/physiology , Postoperative Period , Predictive Value of Tests , Prognosis , Reticulocyte Count , Reticulocytes/physiology , Transplantation, AutologousABSTRACT
Oxidative stress and reticulocyte maturity index (RMI) were studied in 27 patients who underwent bone marrow transplantation (BMT). Plasmatic lipoperoxide levels of those patients with unfavorable evolution were significantly increased on days 12-14 post-transplant (median 1.83 microM, range 0.78-5.82) compared with preconditioning levels (median 1.05 microM, range 0.36-1.84) (p < 0.05). Patients with favorable evolution revealed significantly higher lipoperoxide levels during conditioning regime (median 1.42 microM, range 0.31-4.50) (p < 0.05). Starting from the 3rd post-transplant week a significant and continuous decrease was observed, with a median of 0.77 microM (range 0.21-1.48 p < 0.05) for the 3rd, and a median of 0.60 microM (range 0.11-1.48 for the 4th week (p < 0.01). A significant increase in total antioxidant activity was observed in the three patients who died up to the 35 days post-transplant. Recovery of bone marrow function was detected by RMI after a median time of 17 days (range 11-24) post-allogeneic transplantation. The threshold established for absolute neutrophil count was achieved after a median of 21 days (range 14-28) (p < 0.001). An increase of plasma lipoperoxides on days 12-14 post-transplant may be a predictive value of unfavourable evolution. RMI was the earlier indicator of engraftment in allogeneic BMT.
ABSTRACT
El estrés oxidativo y el índice de madurez reticulocitaria (IMR) fueron estudiados en 27 pacientessometidos a trasplante de médula ósea (TMO). En los pacientes con evolución no favorable, los lipoperóxidos mostraron un incremento entre el día 12-14 postransplante (mediana 1.83 AM rango 0.78-5.82) con respecto al precondicionamiento (mediana 1.05 AM rango 0.36-1.84 p<0.05).Los pacientes con evolución favorable revelaron un incremento de lipoperóxidos durante el condicionamiento (p<0.05) (mediana: 1.42 AM rango: 0.31-4.50) y un descenso significativo durante la tercera semana (mediana 0.77 AM rango 0.21-1.48) y cuarta semana postrasplante (mediana 0.60 AM rango 0.11-1.48) con respecto a los valores precondicionamiento (p<0.05 y p<0.01 respectivamente). La actividad antioxidante total aumentó significativamente en los pacien-tes que evolucionaron al óbito dentro de los 35 días postrasplante (n:3). El IMR reveló engraftment en los TMOalogénicos en el día 17 (rango 11-24) vs neutrófilos: día 21 (rango14-28 p<0.001). El incremento de lipoperóxidosdurante los días 12-14 postrasplante fue predictor de evolución no favorable. El IMR resultó el más tempranodetector de engraftment en TMO alogénicos (AU)
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Bone Marrow/physiology , Bone Marrow Transplantation , Whole-Body Irradiation , Bone Marrow/metabolism , Bone Marrow/radiation effects , Prognosis , Oxidative Stress , Reticulocyte Count , Reticulocytes/physiology , Lipid Peroxides/blood , Lipid Peroxides/metabolism , Postoperative Period , Neutrophils/physiology , Bone Marrow Cells , Predictive Value of Tests , Transplantation, AutologousABSTRACT
El estrés oxidativo y el índice de madurez reticulocitaria (IMR) fueron estudiados en 27 pacientessometidos a trasplante de médula ósea (TMO). En los pacientes con evolución no favorable, los lipoperóxidos mostraron un incremento entre el día 12-14 postransplante (mediana 1.83 µM rango 0.78-5.82) con respecto al precondicionamiento (mediana 1.05 µM rango 0.36-1.84 p<0.05).Los pacientes con evolución favorable revelaron un incremento de lipoperóxidos durante el condicionamiento (p<0.05) (mediana: 1.42 µM rango: 0.31-4.50) y un descenso significativo durante la tercera semana (mediana 0.77 µM rango 0.21-1.48) y cuarta semana postrasplante (mediana 0.60 µM rango 0.11-1.48) con respecto a los valores precondicionamiento (p<0.05 y p<0.01 respectivamente). La actividad antioxidante total aumentó significativamente en los pacien-tes que evolucionaron al óbito dentro de los 35 días postrasplante (n:3). El IMR reveló engraftment en los TMOalogénicos en el día 17 (rango 11-24) vs neutrófilos: día 21 (rango14-28 p<0.001). El incremento de lipoperóxidosdurante los días 12-14 postrasplante fue predictor de evolución no favorable. El IMR resultó el más tempranodetector de engraftment en TMO alogénicos
