RESUMO
Disorders in the hypothalamic-pituitary-adrenal axis are associated with the pathogenesis of Trypanosoma cruzi infection. During the acute phase of this disease, increased levels of circulating glucocorticoids (GCs) correlate with thymic atrophy. Recently, we demonstrated that this phenomenon is paralleled by a decrease of prolactin (PRL) secretion, another stress hormone that seems to counteract many immunosuppressive effects of GCs. Both GCs and PRL are intrathymically produced and exhibit mutual antagonism through the activation of their respective receptors, GR, and PRLR. Considering that GCs induce apoptosis and inhibit double-positive (DP) thymocyte proliferation and that PRL administration prevents these effects, it seems plausible that a local imbalance of GR-PRLR crosstalk underlies the thymic involution occurring in acute T. cruzi infection. In this respect, preserving PRLR signaling seems to be crucial for protecting DP from GC-induced apoptosis.
Assuntos
Doença de Chagas/imunologia , Doença de Chagas/patologia , Timo/patologia , Animais , Apoptose/imunologia , Atrofia , Glucocorticoides/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Camundongos , Neuroimunomodulação , Sistemas Neurossecretores/imunologia , Prolactina/imunologia , Receptor Cross-Talk , Receptores de Glucocorticoides/imunologia , Receptores da Prolactina/imunologia , Transdução de Sinais , Estresse Fisiológico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Timo/imunologiaRESUMO
Monoclonal antibody (MAb) termed R7B4 was generated throughout the idiotypic-anti-idiotypic network from mice immunized with human and bovine growth hormones (GH). The Ab was selected on the basis that it did not recognize human GH (hGH) neither insolubilized nor in solution but inhibited 125I-hGH binding to receptors from rat and rabbit liver and from Nb2-cell membranes. Since it inhibited Nb2-cell mitogenesis stimulated by hGH, prolactins or placental lactogens, MAb R7B4 behaved as an antagonist of lactogenic hormones. Furthermore, the Ab impaired proliferative activity of interleukin 2 (IL-2) on Nb2 cells as well as growth of 7TD1 cells, an interleukin 6 (IL-6) dependent hybridoma not expressing GH receptors. Biotin-labeled MAb R7B4 specifically bound to rat liver microsomes, and the Ab was able to recognize Nb2 and 7TD1-cell membranes as shown by flow cytometry experiments. However, MAb binding was not hampered by hGH, indicating that the Ab did not mimic GH binding site to receptors. Immunoblot assays indicated that rat and rabbit liver as well as Nb2-cells membrane antigens recognized by MAb R7B4 were similar to those revealed by a MAb directed to prolactin receptors. In addition, MAb R7B4 was able to detect two bands probably corresponding to the somatogenic receptor in rabbit liver microsomes as well as three different proteins in 7TD1-cells showing molecular weights similar to those of the IL-6 receptor complex. Results suggest that MAb R7B4 is directed to an epitope shared by receptors for lactogenic and somatogenic hormones, IL-2 and IL-6. To our knowledge, these data are the first experimental evidence of the existence of structural similarity between some of the receptors grouped in the cytokine receptor superfamily.
Assuntos
Anticorpos Monoclonais/metabolismo , Epitopos/imunologia , Receptores de Interleucina-2/imunologia , Receptores de Interleucina-6/imunologia , Receptores da Prolactina/imunologia , Receptores da Somatotropina/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Ligação Competitiva , Bovinos , Células Cultivadas , Epitopos/metabolismo , Citometria de Fluxo , Humanos , Hibridomas , Imunização , Immunoblotting , Técnicas Imunoenzimáticas , Insulina/metabolismo , Interferons/metabolismo , Radioisótopos do Iodo/metabolismo , Camundongos , Microssomos Hepáticos/metabolismo , Ratos , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-6/metabolismo , Receptores da Prolactina/metabolismo , Receptores da Somatotropina/metabolismo , Ovinos , Células Tumorais CultivadasRESUMO
En el presente trabajo se evidencia el papel de esta hormona en la proliferación linfocitaria, la inducción de receptores para la interleuquina-2 en la superficie de los linfocitos, y la producción por parte de estas células, de una mólecula prolactin-like, así como otros aspectos que acentúan los novedosos efectos de la PRL sobre el sistema inmune
Assuntos
Linfócitos B/imunologia , Sistema Imunitário/fisiologia , Prolactina/imunologia , Receptores de Interleucina-2/imunologia , Receptores da Prolactina/imunologia , Linfócitos T/imunologiaRESUMO
Tradicionalmente se había considerado al sistema inmunitario como autónomo; sin embargo, pruebas recientes han demostrado que existen comunicaciones bidireccionales entre el sistema inmunitario y el neuroendócrino. Hay influencia de las hormonas gonadales, tiroideas, suprarrenales y pituitarias. De entre éstas, la prolactina ha sobresalido como potencial blanco para modificar la respuesta inmunitaria en algunos estados de enfermedad