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1.
Transfus Clin Biol ; 15(1-2): 23-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18502676

RESUMEN

Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent. We now know that SS RBCs express numerous adhesion molecules, and that many of these can undergo activation. SS RBCs exposed briefly to epinephrine show markedly increased adhesion to both laminin and endothelial cells. In vivo, infusion of epinephrine-activated but not unstimulated SS RBCs causes RBC adhesion, vaso-occlusion, organ trapping, and shortened RBC survival in the circulation. Epinephrine treatment of SS RBCs before infusion also induces adhesion of murine leukocytes to vascular walls. Indeed, in vitro, SS RBCs can activate leukocyte adhesion and cytokine production. We now have demonstrated both in vitro and in vivo evidence for the importance of RBC signaling and have also shown that SS RBC adhesion is determined by genetic polymorphisms in the signaling pathway that activates adhesion. These advances will hopefully lead to new therapeutic modalities for sickle cell disease.


Asunto(s)
Anemia de Células Falciformes/fisiopatología , Moléculas de Adhesión Celular/fisiología , Eritrocitos/fisiología , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/genética , Animales , Adhesión Celular/efectos de los fármacos , Células Endoteliales/fisiología , Humanos , Laminina/fisiología , Leucocitos/fisiología , Ratones , Polimorfismo Genético , Transducción de Señal
2.
Transfus Clin Biol ; 13(1-2): 44-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16564726

RESUMEN

The LW blood group antigen glycoprotein, although part of the Rh macromolecular complex, is nonetheless a member of the intercellular adhesion molecule (ICAM) family. Thus, while it is only rarely clinically important in the setting of transfusion and pregnancy, LW is likely to contribute to red cell adhesion in a variety of settings, including during hematopoiesis, as well as in vascular disorders. The best documentation of a pathophysiological role for LW in human disease is in sickle cell disease, where it contributes to red cell adhesion to endothelial cells and the development of vaso-occlusion, the hallmark of that disease. LW may also contribute to other intravascular processes, such as both venous and arterial thrombosis, due to its ability to interact with both activated platelets as well as leukocytes. The evidence that LW itself can undergo activation on red cells holds promise that pharmacotherapeutic maneuvers may be found to prevent such pathophysiologic interactions.


Asunto(s)
Moléculas de Adhesión Celular/fisiología , Alelos , Anemia de Células Falciformes/fisiopatología , Antígenos de Grupos Sanguíneos/genética , Plaquetas/metabolismo , Adhesión Celular/fisiología , Moléculas de Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular/genética , Cromosomas Humanos Par 9/genética , AMP Cíclico/fisiología , Endotelio Vascular/patología , Epinefrina/farmacología , Eritrocitos/metabolismo , Eritrocitos/fisiología , Humanos , Integrina alfaV/metabolismo , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Fosforilación/efectos de los fármacos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Polimorfismo de Nucleótido Simple , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores Adrenérgicos beta/fisiología , Sistema del Grupo Sanguíneo Rh-Hr/fisiología , Transducción de Señal/efectos de los fármacos , Trombosis/fisiopatología
3.
Bull Cancer ; 80(8): 674-9, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8204947

RESUMEN

The possibility of targeting LAK cells to the tumor by arming them with monoclonal antibodies directed against tumor associated antigens was tested in a rat model of colon carcinoma. Peritoneal carcinomatosis was generated by injection of cloned tumor cells and 111In-labeled LAK cells were injected in the tail vein after preincubation with the monoclonal antibodies themselves. It appeared that the antibodies did not significantly improve tumor targeting of LAK cells, most of the radioactivity being recovered in the spleen, the liver, the kidney or the lung, and only a small fraction in the tumor.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias del Colon/terapia , Citotoxicidad Inmunológica , Células Asesinas Activadas por Linfocinas/metabolismo , Neoplasias Experimentales/terapia , Animales , Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias Experimentales/inmunología , Ratas
4.
In Vitro Cell Dev Biol ; 29A(2): 140-4, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8473271

RESUMEN

We examined the effects of all-trans retinoic acid (RA) on alpha(1-->2) fucosyltransferase activity and sensitivity to LAK-mediated cytotoxicity in two rat colon carcinoma cell lines differing by their glycosylation state and their tumorigenic potential. RA induced a decrease in alpha(1-->2) fucosyltransferase activity in the more tumorigenic variant PROb. Fucosyltransferase mRNA levels were not affected by RA treatment in PROb cells, suggesting a posttranscriptional control. This inhibition was accompanied by a decreased expression of fucosylated membrane glycoconjugates and by a significant increase in the sensitivity to LAK-mediated cytotoxicity. REGb cells, which exhibited a very low enzymatic activity and very few fucosylated glycoconjugates, were more sensitive to LAK-lysis than PROb cells and were not affected by RA treatment.


Asunto(s)
Citotoxicidad Inmunológica/efectos de los fármacos , Fucosiltransferasas/metabolismo , Células Asesinas Activadas por Linfocinas/inmunología , Tretinoina/farmacología , Adenocarcinoma , Animales , Secuencia de Bases , Northern Blotting , Células Clonales , Neoplasias del Colon , Fucosiltransferasas/genética , Cinética , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/aislamiento & purificación , Ratas , Bazo/inmunología , Células Tumorales Cultivadas , Galactósido 2-alfa-L-Fucosiltransferasa
5.
Int J Cancer ; 52(6): 934-40, 1992 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-1459734

RESUMEN

We analyzed several factors which could influence the immunogenicity of colon tumor cells, using a series of clones derived from a single chemically induced rat adenocarcinoma cell line. These clones display variable tumorigenic potential in syngeneic immunocompetent animals, and it has been established that in this model the tumorigenicity of the cells depends on their ability to escape immune surveillance. The results show an absence of relationship between tumorigenicity and expression of MHC-class-I antigens, cell adhesion to rat fibroblasts or fibroblast extracellular matrix. The secretion of latent and active TGF beta I appeared to be quite variable from one clone to the other, but was unrelated to tumorigenicity. Unexpectedly, some regressive clones produced elevated levels of this cytokine, suggesting that in this model, spontaneous secretion of TGF beta I is not sufficient to impair the immune system of the host. In contrast, the more tumorigenic clones were more resistant than less tumorigenic ones to cytotoxicity mediated by NK or LAK cells. They also showed arrest of cell proliferation after reaching confluence, something not observed in the less tumorigenic clones. Finally, the strongest relationship with tumorigenicity was found for expression of blood-group carbohydrate antigens. Increased expression of blood-group-H antigen and, conversely, decreased expression of beta-galactoside precursors of this antigen correlated with increased tumorigenicity.


Asunto(s)
Adenocarcinoma/inmunología , Neoplasias del Colon/inmunología , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Animales , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Adhesión Celular , División Celular , Células Clonales , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Citometría de Flujo , Fucosiltransferasas/análisis , Ratas , Análisis de Regresión , Factor de Crecimiento Transformador beta/análisis , Células Tumorales Cultivadas , Galactósido 2-alfa-L-Fucosiltransferasa
6.
Cell Immunol ; 210(2): 96-105, 2001 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-11520076

RESUMEN

Recognition of melanoma antigens by HLA class-II-restricted CD4(+) T lymphocytes has been investigated. Two cytotoxic CD4(+) T cell lines were established by stimulating PBLs from a melanoma patient with either parental or IFN-gamma-transduced autologous tumor cells. These T cells secreted IL-4, but not IL-2, IFN-gamma, or TNF-beta, in response to the autologous melanoma cells, suggesting that they belong to the Th2 subtype. Their cytotoxicity was directed against the IFN-gamma-transduced melanoma cells and was HLA-DR-restricted. The autologous and two allogeneic IFN-gamma-modified melanoma cell lines shared melanoma antigen(s) presented in the context of HLA-DR15. HLA-DR15(+) nonmelanoma cells were resistant targets indicating that the shared antigen(s) is melanoma associated. Parental autologous and HLA-DR-matched allogeneic melanoma cell lines, displaying low levels of HLA-DR antigens, induced Th2 proliferation and cytokine release, but were insensitive to lysis prior to upregulation of HLA-DR and Fas antigens by IFN-gamma. Cytolysis was inhibited by anti-HLA-DR and by anti-Fas antibodies, suggesting that the cytolysis is mediated via the Fas pathway. While small amounts of HLA-DR15 molecules on melanoma cells are sufficient for Th2 proliferation and cytokine release, higher amounts of HLA-DR15 and the expression of Fas are required for CD4(+)-mediated lysis.


Asunto(s)
Antígenos de Neoplasias/inmunología , Antígenos HLA-DR/inmunología , Melanoma/inmunología , Linfocitos T Citotóxicos/inmunología , Células Th2/inmunología , Receptor fas/inmunología , Linfocitos B/inmunología , Línea Celular Transformada/inmunología , Citotoxicidad Inmunológica , Fibroblastos/inmunología , Subtipos Serológicos HLA-DR , Humanos , Interferón gamma/metabolismo , Interferón gamma/farmacología , Interleucina-2/farmacología , Interleucina-4/farmacología , Activación de Linfocitos , Linfocinas/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/metabolismo , Células Th2/efectos de los fármacos , Células Th2/metabolismo , Transfección , Células Tumorales Cultivadas/inmunología , Factor de Necrosis Tumoral alfa/farmacología
7.
Epithelial Cell Biol ; 1(4): 168-76, 1992 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1307947

RESUMEN

We examined the fibronectin-adhesive properties of clones from a rat colonic cell line exhibiting distinct tumorigenicity in a syngeneic host. These cells were originally selected on the basis of differential adhesion to plastic surfaces. The TR cell line, when injected subcutaneously, forms a tumour which grows progressively and gives off metastases, whereas the TS cell line forms a small tumour which regresses within a few weeks. The regression is largely mediated by immunological factors and involves a fibroblastic reaction. REGb, a clone from the TS subline, adhered better to fibronectin or RGDS tetrapeptide than did PROb, a clone from the TR subline. However, there was little binding to the RGD tripeptide with either clone. The degree of adhesion was dependent on time and substrate concentration. After 6 h of incubation, 38% and 55% respectively of PROb and REGb cells bound to plates coated with 10 micrograms/ml fibronectin. Adhesion of both clones to fibronectin was inhibited to various degrees when cells were preincubated with RGDS, GRGDS or GRADSPK peptides, whereas other synthetic peptides such as RGD, GRGD or GRGFSPK were ineffective. Binding experiments using 125I-labelled fibronectin showed 39,000 fibronectin receptor sites on REGb cells but only 17,000 on PROb cells. Flow cytometry analysis using both anti-alpha 5 and anti-beta 1 integrins showed more fibronectin receptor sites on REGb than on PROb cells. Both approaches were in accordance with the higher adhesiveness of the REGb clone to fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Fibronectinas/metabolismo , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/secundario , Secuencia de Aminoácidos , Animales , Adhesión Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Datos de Secuencia Molecular , Trasplante de Neoplasias , Oligopéptidos/química , Oligopéptidos/metabolismo , Ratas , Receptores de Fibronectina/metabolismo
8.
Int J Cancer ; 53(3): 409-17, 1993 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-8428794

RESUMEN

NK and LAK cells which are able to lyse tumor target cells in an MHC-unrestricted manner are not equally effective against targets of the same nature. In the case of colorectal tumors, some cells are highly sensitive, whereas others are resistant to NK and can even be quite resistant to LAK-mediated lysis. In the present paper, we tried to correlate the stage of differentiation of 17 human colorectal tumor cell lines with their NK- or LAK-cell susceptibility. It was observed that NK cells killed colorectal target cells independently from their stage of differentiation defined according to histopathological criteria from xenografting in nude mice. NK susceptibility was not correlated either with in vitro-defined criteria of differentiation, such as cell polarity and morphology, brush-border enzyme expression and CEA production. A LAK-resistant HT-29 sub-line (HT-29 LAK) was selected which could not be distinguished from HT-29 in terms of features of differentiation. It was further observed that HT-29 Glc-/+ cell line, a highly differentiated enterocytic-like variant of HT-29, obtained after glucose starvation, was killed by LAK cells as efficiently as the moderately differentiated parental HT-29, and that Caco-2 cells, which differentiate spontaneously after confluence in standard culture conditions, were equally sensitive to NK-mediated lysis whatever their stage of differentiation. In contrast, HT29 MTX10(-5), a highly differentiated mucus-secreting variant of HT29 obtained by methotrexate selection, was much more resistant to LAK cells than parental HT29 cells.


Asunto(s)
Carcinoma/patología , Neoplasias del Colon/patología , Células Asesinas Activadas por Linfocinas/inmunología , Células Asesinas Naturales/inmunología , Animales , Carcinoma/inmunología , Diferenciación Celular , Neoplasias del Colon/inmunología , Citotoxicidad Inmunológica , Humanos , Inmunidad Celular , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Células Tumorales Cultivadas
9.
Int J Cancer ; 52(4): 609-18, 1992 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-1399144

RESUMEN

The susceptibility to natural-killer-cell lysis and expression of histo-blood-group antigens of 2 clones from a rat colon adenocarcinoma, of variants derived from them and of 17 human colon carcinoma cell lines were assessed in an attempt to determine if the major glycosidic tissue antigens of epithelial cells could influence the NK susceptibility of tumor target cells of epithelial origin. The rat REGb clone, which is relatively NK-sensitive, expressed higher levels of precursor structures T and Tn and lower levels of H antigenic determinants than the PROb clone, which displays higher resistance to NK-cell lysis. Cell variants were obtained from these 2 clones; it appeared that whether the cell variants were selected on the basis of expression of a blood-group antigenic determinant or on the basis of altered susceptibility to NK-cell lysis, there was a link between increased resistance and higher expression of cell-surface A and H histo-blood-group antigens, or conversely, between increased sensitivity and higher expression of precursor structures. Similar conclusions were obtained upon study of the human cell lines, since a significant correlation was found between the level of expression of T or Tn antigens and sensitivity to NK-cell lysis. A significant relationship was found between the expression of Lewis antigens and increased resistance to NK-cell-mediated cytotoxicity.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores , Antígenos de Grupos Sanguíneos/inmunología , Neoplasias del Colon/inmunología , Citotoxicidad Inmunológica , Células Asesinas Naturales/inmunología , Sistema del Grupo Sanguíneo ABO/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias del Colon/patología , Glicosilación , Humanos , Células Asesinas Activadas por Linfocinas/inmunología , Antígenos del Grupo Sanguíneo de Lewis/inmunología , Células Tumorales Cultivadas
10.
Int J Cancer ; 50(4): 659-64, 1992 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-1537634

RESUMEN

The sensitivity of colorectal tumors to NK-cell-mediated cytotoxicity and their expression of major histocompatibility complex (MHC) class-I antigens were studied in an attempt to determine whether such antigens play a role in the susceptibility of colorectal tumors to NK-cell lysis. In a rat colon-carcinoma model, 2 clones differing in their sensitivity to NK-cell-mediated cytotoxicity were tested for class-I expression; it was seen that the more sensitive cells (REGb) expressed less class-I products than did the resistant cells (PROb). However, when MHC class-I antigen expression was increased by IFN-gamma treatment, no change in NK-cell lysis was found with the PROb cells, while an increase in cytotoxicity was obtained with the REGb cells. After in vivo or in vitro selection of NK-resistant REGb cells, we observed in the selected cells an important decrease in RT-I class-I antigen expression. Fifteen different human colorectal cell lines were also studied for HLA class-I expression and NK-cell susceptibility, and no quantitative correlation between these 2 features was seen. However, cell lines which were deficient in HLA class-I antigens were more sensitive than class-I-positive cells.


Asunto(s)
Carcinoma/inmunología , Neoplasias del Colon/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Células Asesinas Naturales/inmunología , Animales , Citotoxicidad Inmunológica , Antígenos HLA/inmunología , Humanos , Inmunidad Celular , Células Asesinas Activadas por Linfocinas/inmunología , Ratas , Células Tumorales Cultivadas
11.
Scand J Immunol ; 46(1): 27-34, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9246205

RESUMEN

The influence of the epithelial mucin MUC1 on T cell-mediated lysis was analysed using lymph node lymphocytes (LNL) from patients with colorectal carcinoma. LNL were stimulated with allogeneic, MUC1-transfected B cells and the bulk cultures were cloned. Alloreactive cytotoxic T cell clones were obtained which preferentially lysed MUC1-expressing targets. The majority was CD4+ and MHC-class II-restricted, and a minor group was CD8+ and MHC-class I-restricted. All the clones expressed CD3 and TCR alpha beta, and were CD56-. The capacity to preferentially kill MUC1-expressing targets was stable in several clones for up to 6 months in culture. The enhancing effect of MUC1 on the lysis was investigated in more detail. It was only seen after inhibition of O-linked glycosylation in the targets. Furthermore, this effect was completely abrogated by the monoclonal antibody 3C9, directed against the Thomsen-Friedenreich antigen (T-antigen, Gal beta 1-3GalNAc bound alpha 1-3 to Ser/Thr) as well as by the soluble disaccharide Gal beta 1-3GalNAc, but not by other similar disaccharides. The authors conclude that in their system the preferential killing of MUC1-expressing targets is due to the recognition of an internal carbohydrate epitope accessible on under-glycosylated MUC1, possibly T-antigen, by an auxiliary receptor molecule on T cells.


Asunto(s)
Carcinoma/inmunología , Neoplasias Colorrectales/inmunología , Citotoxicidad Inmunológica , Mucina-1/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Anticuerpos Antineoplásicos/inmunología , Carbohidratos/inmunología , Células Cultivadas , Humanos , Inmunidad Celular , Inmunofenotipificación
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