ABSTRACT
La arteritis de la temporal, clasificada como una vasculitis que compromete vasos de gran y mediano calibre, debe ser considerada como una emergencia médica, dado el potencial de causar ceguera y accidentes vasculares. La lesión típica corresponde a granulomas en la pared vascular, los que están constituidos por macrófagos y célulasT CD4+. Éstos se activan en la adventicia, luego de interactuar con las células dendríticas nativas. La injuria tisular es mediada por diversos subtipos de macrófagos, los que ejercen las diferentes funciones efectoras. El daño que domina en la capa media resulta del estrés oxidativo y determina la apoptosis de las células musculares lisas y la nitración de las endoteliales. Por otro lado, factores de crecimiento derivados de macrófagos determinan la hiperplasia intimal y la consecuente oclusión luminal. Las manifestaciones clínicas se relacionan estrechamente con el sitio isquémico. El tratamiento de elección son los corticoides sistémicos, los cuales pueden asociarse a inmunosupresores como también con agentes biológicos.
Temporal arthritis, which is classified as a large-and medium-caliber vessel vasculitis, should be considered as a medical emergency, given its potential to cause blindness and strokes. The injury typically corresponds to granulomas in the vascular wall, which are composed of macrophages and CD4+ T cells. They are activated in the adventitia, after interacting with native dendritic cells. Immunopathological mechanisms involve different subtypes of macrophaesges, which exert different effector functions. Damage that prevails within the median layer is secondary to oxidative stress and triggers apoptosis of smooth muscle cells and nitration of endothelial cells. On the other hand, growth factors derived from macrophages determine intimal hyperplasia and subsequent luminal occlusion. Clinical manifestations are closely related to the ischemic site. The treatment of choice is systemic corticosteroids, which can be associated with immunosuppressive drugs as well as biological agents.
Subject(s)
Humans , Giant Cell Arteritis/immunology , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/metabolism , Giant Cell Arteritis/drug therapy , Interferon-alpha/metabolism , /immunology , /metabolism , Macrophages/immunology , Macrophages/metabolism , Risk Factors , Signs and SymptomsABSTRACT
CD4+CD56+ lineage negative malignancy has recently been considered as plasmacytoid dendritic cell (PDC) leukemia/lymphoma. We investigated immunophenotypic and functional characterizations of PDC leukemic cells in one case. Lineage markers were all negative except partially positive CD11c and positive CD117, indicating malignant cells were leukemic PDCs coexpressing myeloid and progenitor cell surface antigens. Leukemic PDCs cultured with IL-3 increased in size and expression of CD11c, CD40 and HLA-DR, although the cells cultured with IL-2 or GM-CSF showed little proliferation. Furthermore, CD40 ligation after IL-3 stimulation yielded morphological changes such as expression of dendritic process. These findings showed that malignant cells were consistent with leukemic PDCs. However, secretion of interferon-alpha was not detected in leukemic PDCs with the stimulation of CpG ODN or inactivated herpes simplex virus-1.
Subject(s)
Aged , Antigens, CD/analysis , Cell Lineage , Dendritic Cells/immunology , Female , Humans , Immunophenotyping , Interferon-alpha/metabolism , Leukemia/immunology , Lymphokines/immunologyABSTRACT
Abnormal production of interferon alpha (IFN-a) has been found in certain autoimmune diseases and can be also observed after prolonged therapy with IFN-a. IFN-a can contribute to the pathogenesis of allograft rejection in bone marrow transplants. Therefore, the development of IFN-a inhibitors as a soluble receptor protein may be valuable for the therapeutic control of these diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and 261-410 (P2) of the extracellular domain of subunit 1 of the interferon-a receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides and of their respective antibodies were evaluated using antiproliferative and antiviral assays. Expression of P1 and P2 polypeptides was achieved by transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG induction. P1 and P2 were purified by serial sonication steps and by gel filtration chromatography with 8 M urea and refolded by dialysis. Under reducing SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa, respectively. Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. P1 and P2 and their respective polyclonal antibodies were able to block the antiproliferative activity of 6.25 nM IFN-aB on Daudi cells, but did not block IFN-aB activity at higher concentrations (>6.25 nM). On the other hand, the polypeptides and their respective antibodies did not inhibit the antiviral activity of IFN-aB on Hep 2/c cells challenged with encephalomyocarditis virus.
Subject(s)
Humans , Animals , Cattle , Mice , Antiviral Agents/metabolism , Escherichia coli , Interferon Type I/metabolism , Interferon-alpha/metabolism , Peptides , Receptors, Interferon , Statistics, NonparametricABSTRACT
En los últimos años la inmunoterapia ha tomado un gran auge debido, primordialmente, a la variedad de alternativas descritas, fundamentadas en una gran cantidad de estudios clínicos, lo que ha permitido que enfermedades aparentemente poco complicadas, pero cuya resolución es frecuentemente problemática, como las infecciones recurrentes de las vías respiratorias, hasta enfermedades crónicas como tuberculosis, lepra, colagenopatías y enfermedades malignas, etc., ahora puedan tener un mejor pronostico. Es importante resaltar la importancia de conocer las características farmacologicas de estos medicamentos, así como sus indicaciones precisas. con el fin de no caer en el mal uso de los mismos y poder ofrecer a los pacientes un recurso valioso y eficaz de cara al nuevo milenio