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Biomedical subjects

R Solana

Publications and source records attributed to R Solana.

At least 55 records · Page 3Linked to original sources

Identification of a tumour factor inducing resistance to NK cell lysis.

The mechanisms involved in the resistance or susceptibility of tumour cells to NK cytotoxicity are poorly understood. The role of different molecules on the target cell surface which could act as recognition elements by NK effectors has been postulated. However, there are also some tumour cell lines which release factors capable of inhibiting NK cytotoxicity. This paper presents a new factor (NK-RIF), produced and released by different tumour cell lines, making K562 resistant to NK lysis without affecting the cytotoxic function of NK effector cells. This soluble factor is shown to be thermolabile, non-dialyzable and to have a molecular weight of 36,000 daltons. It does not block the binding capacity of the target and effector cells, nor does it affect target susceptibility to LAK or cytotoxic T-cells.

Adenocarcinoma↗

Macrophage and lymphocyte antibody-dependent cellular cytotoxicity in spontaneous leukemogenesis of AKR/J mice.

Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by peritoneal macrophages and splenic lymphocytes was studied in young (15 weeks) and old (45 +/- 5 weeks) preleukemic AKR/J mice and leukemic (55 +/- 5 weeks) AKR/J mice. This strain spontaneously develops a virally induced T cell leukemia-lymphoma between the ages of 32 and 48 weeks. The peritoneal macrophages from the AKR/J leukemic and old preleukemic mice showed an impaired ADCC when compared with their respective age and tumor-free BALB/c controls and with young preleukemic AKR/J mice. Young and old preleukemic AKR/J mice and their respective controls had similar ADCC values with respect to splenic lymphocytes, whereas an impaired ADCC was observed by the splenic cells from leukemic AKR/J mice. The possibility of using ADCC mediated by macrophages as a test to detect the onset of the leukemic process is discussed.

Animals↗

Natural killer susceptibility of brain tumor cell lines inversely correlates with the degree of cell differentiation and not with the level of human histocompatibility antigen expression.

The purpose of this paper is to investigate the natural killer (NK) sensitivity of 15 cell lines derived from human brain tumors expressing different levels of major histocompatibility complex (MHC) antigens. Although it has recently been reported that NK susceptibility varies inversely with target cell class-I human leukocyte antigen (HLA) expression, our results show no correlation between class-I HLA, class-II HLA or beta 2-microglobulin expression on target cells and NK sensitivity, whereas a significant inverse correlation between NK susceptibility and the degree of tumor cell differentiation has been found. Thus, poorly differentiated tumor cells are highly susceptible to NK lysis, whereas well-differentiated ones are NK resistant. These results suggest that sensitivity to lysis by NK cells of cell lines derived from human brain tumors is primarily determined by the stage of differentiation and not by the level of MHC antigen expression on target cell.

Brain Neoplasms↗

HLA-DQ molecular heterogeneity in HLA-DR4-Dw4 consanguineous cell lines.

Two-dimensional gel analysis (NEPHGE) of the molecules precipitated by the HLA-DR monomorphic antibody L243 showed a single and identical alpha chain spot from two consanguineous cell lines, BM14 and MCF. The latter was derived from a rheumatoid arthritis patient. No apparent structural polymorphism of the HLA-DR beta chains was detected. The data suggests that the HLA-DR4 haplotype expresses one alpha chain and up to four beta chains. The electrophoretic pattern of the HLA-DQ molecules precipitated with the monomorphic antibody TU22 revealed clear differences between BM14 and MCF. These differences were mainly in the beta chain profiles. Four acidic beta chains were found with the MCF cell line wheras only three beta chains at different isoelectric points were found with the BM14 cell line. The data obtained in this study argue for a considerable heterogeneity of the HLA-DQ antigens detected at the molecular level.

Arthritis, Rheumatoid↗

Differential expression of HLA-DR and HLA-DQ antigens on normal cells of the myelomonocytic lineage.

We have previously shown that HLA-class II antigens have a differential expression on acute myeloblastic leukaemia (AML) blasts. These cells express HLA-DR molecules but the HLA-DQ antigens are undetectable. In this paper we study the expression of HLA-DR and HLA-DQ antigens, using monoclonal antibodies (MoAbs), on normal cells of the myelomonocytic lineage: the common myelomonocytic progenitor (CFU-GM) and the monocytes, by techniques of inhibition of CFU-GM growth and double immunofluoroscence, respectively. The results show that HLA-DR and HLA-DQ antigens are differentially expressed on normal myelomonocytic cells. While HLA-DR molecules are expressed on CFU-GM and on the majority of peripheral blood monocytes, HLA-DQ antigens are not expressed on CFU-GM and only present on a subpopulation of monocytes. This data further confirms that HLA-DR and HLA-DQ molecules are coded by different genes with independent regulation of the gene expression not only on myeloid leukaemias but also on normal cells of the myelomonocytic lineage.

Adult↗

Alterations in CFU-GM growth in preleukaemic and leukaemic AKR/J mice.

The behaviour of committed CFU-GM bone marrow cells was investigated in leukaemic and preleukaemic AKR/J mice. The number of bone marrow CFU-GM decreased in the leukaemic stage of spontaneous AKR/J leukaemia. The addition of AKR/J leukaemic cells inhibited CFU-GM growth from normal target bone marrow. The bone marrow CFU-GM growth was also reduced in late preleukaemic AKR/J mice, whereas no modification in the CFU-GM number in early preleukaemic animals was found.

Animals↗

Effect of Fiblaferon-L on the human immune system.

The effect of a new commercial interferon (Fiblaferon L) on the human immune system was studied. Different experiments were performed on human peripheral blood in vitro, in order to observe: (a) the phagocytic capacity of polymorphonuclear leukocytes (PMNL) and monocytes; (b) monocyte adherence index, and (c) percentage of antibody-dependent cellular cytotoxicity (ADCC) against chicken red blood cells (CRBC). Fiblaferon L enhanced all these functions.

Animals↗

Effect of phorbol ester TPA on macrophage metabolic activity.

Metabolically active macrophages are known to play a role in tumor immune surveillance, not only as effector cells but also as collaborators in T cell mediated immune response. The present work reports that non-toxic concentrations of the tumor promoter TPA, stimulate the adherence of murine peritoneal macrophages after short time incubation, while TPA pretreatment for periods longer than 4 hrs suppresses phagocytosis, RNA and protein synthesis by these cells. Although inhibition of macrophage metabolic activity could play an additional role in tumor promotion, the enhancing and depressing effects of TPA on the immune system must be weighed before it can be assumed that TPA acts in vivo primarily to depress the immune system.

Animals↗

Depressed lymphoproliferative response in mixed leukocyte reaction after Mis-locus alloimmunization.

The proliferation of BALB/C lymphocytes preimmunized with Mis or H-2 incompatible cells in response to alloantigens was studied. The results show that preimmunization with Mis-incompatible spleen cells inhibits the lymphoproliferative response against alloantigens whereas preimmunization with H-2 incompatible spleen cells enhances it. It is suggested that Mis coded determinants activate suppressor mechanisms responsible for the unresponsiveness of these preimmunized lymphocytes against alloantigens.

Animals↗

Soluble suppressor of T cell proliferation in primary in vitro response to murine minor histocompatibility antigens.

Normal mouse lymphocytes are not capable of mounting a primary cytotoxic T cell response to Mls encoded, non H-2, allodeterminants, although a strong lymphoproliferative response is observed in primary MLR between Mls incompatible cells. In this study it is reported that in the supernatant of primary cultures between AKR macrophages and CBA/H lymphocytes (H-2 identical, incompatible for Mls and other minor antigens) a suppressor of T cell proliferation in MLR is detected. By contrast, a suppressor is not detected in supernatants from primary cultures between BALB/C macrophages and CBA/H lymphocytes (H-2 incompatible, Mls identical), B10.BR macrophages and CBA/H macrophages and CBA/H lymphocytes (syngeneic) suggesting that the production of the suppressor factor occurs only when an Mls incompatibility exists. The suppressive activity of the Mls incompatible culture supernatant upon MLR between incompatible macrophages and lymphocytes is neither antigen specific nor Mls or H-2 restricted, nor is it due to an irreversible toxic effect on T lymphocytes or macrophages. The inhibition of T cell proliferation could be explained by inhibition of IL 2 production, by blocking its union to T cells or by a combination of both effects. Our findings could help explain previous observations that lymphocytes from mice preimmunized with Mls incompatible cells have a depressed proliferative response as well as depressed cytotoxicity against alloantigens.

Animals↗

Effect of a new synthetic C-nucleoside (EDTO) on cell proliferation.

The growth of Ehrlich ascite tumour cells obtained from NMRI mice and the proliferative response of T-lymphocytes from human peripheral blood in the presence of a mitogen: phytohemagglutinin (PHA) were studied in order to see what effect 2-(alpha and beta-D-erythrophuranosyl)-6,6-dimethyl-4,5,6,7-tetrahydroindol+ ++-4-one (a new synthetic C-nucleoside) had on cell proliferation. The uptake of 3H-thymidine was used as an index of cellular growth. The results show that although this C-nucleoside did not significantly alter the growth of the tumour cells, it did significantly inhibit the proliferation of T-lymphocytes.

Animals↗

[Effect of a new synthetic cyclic-nucleoside on cell proliferation].

The activity of a new synthetic C-nucleoside upon cell proliferation was tested using mouse Ehrlich ascites tumor cells and PHA-stimulated human blood T lymphocytes. The product did not modify the cancer cells reproduction. Contrarily, it inhibited T lymphocytes proliferation.

Animals↗

Differences in GM-CSF production from mouse peripheral blood and spleen cells stimulated by different lectins.

The capacity of mouse peripheral blood and spleen mononuclear cells to produce GM-CSF or CSA, in response to the stimulation by different mitogens (PHA, PWM and ConA) was studied. Each different kind conditioned medium was tested on target bone marrow from BALB/C mice. A significant decrease in the number of CFU-GM, was observed using peripheral blood conditioned medium stimulated by PHA or ConA in comparison with spleen conditioned medium in response to identical mitogens. When PWM is used as source of GM-CSF, significant differences between spleen and blood conditioned media were not observed. The possible significance of these findings is discussed.

Animals↗

Kinetics and characteristics of murine macrophage-lymphocyte interaction in presence of PHA: appearance of multinucleated giant cells in vitro.

The appearance of cellular associations between macrophages and lymphocytes--which we have denominated macrophage-lymphocyte rosettes--and their kinetic formation in the presence of phytohemagglutinin (PHA) have been studied in B10 A (4R) mice. The greatest number of macrophage-lymphocyte rosettes was found from 6 to 12 hours after incubation with PHA. During this time, 42.38 +/- 10.70 of the total number of macrophages had lymphocytes attached to their membranes. This percentage decreased to 17.33 +/- 2.07% after 24 hours. The activation of macrophages after PHA treatment was tested by the phagocytic capacity of these cells. This activity increased significantly 24 hours after incubation. In our assay, an increase in the appearance of multinucleated giant cells when compared to controls was also observed. When the macrophages were lymphocyte depleted, the appearance of the multinucleated giant cells was significantly lower. The kinetics for these formations are also discussed.

Animals↗

Effect of cyproheptadine on gastric secretion in rats.

The effect of cyproheptadine on serum gastrin and glucose levels and intragastric pH values in male rats was studied. A significant increase in serum gastrin (p less than 0.001) and glucose levels (p less than 0.01) was observed after administration of 4 mg/kg, i.p. of cyproheptadine. Intragastric pH experimented a slight increase (p less than 0.05), and there were no significant changes in the gastrin levels 90 minutes after administration of different doses of cyproheptadine, although the intragastric pH values changes significantly (p less than 0.001) after administration of identical cyproheptadine doses. These results suggest that cyproheptadine stimulates gastrin secretion by an unknown mechanism and that this increase is not related to the alterations observed in serum glucose nor intragastric pH.

Animals↗

Requirement of macrophage metabolic activity for T-lymphocyte activation.

It has been recently demonstrated that macrophages are necessary accessory cells for T-lymphocyte activation by antigens, mitogens and allogenic cells. This paper shows the function of metabolically inactive macrophages in the activation of T-lymphocytes by phytohemagglutinin (PHA). Macrophages inactivated by mitomycin C are unable to collaborate with T-lymphocytes in the development of the proliferative response to PHA indicating that the role of the macrophage in T-lymphocyte activation by mitogens goes beyond insolubilizing it or rendering it more stimulatory by another passive mechanism.

Animals↗

Impaired capacity of the macrophages of newborn mice for T-lymphocyte activation by phytohemagglutinin.

The level of collaboration in phytohemagglutinin (PHA) induced lymphoblastic response by the macrophage of neonatal mice was studied. The results show a diminished response to the mitogen (PHA) when lymphocytes from the spleen of syngeneic adult mice were incubated in the presence of macrophages from neonatal mice as compared to those obtained from cultures performed in the presence of macrophages from adult mice. In both cases the highest response corresponded to the lowest dose of PHA and the lowest amount of macrophages used.

Age Factors↗

[Changes in lymphoblastic transformation in preleukemic AKR/J mice].

The authors investigate the efficacy of the immune system along the AKR/J mouse life span. They employ the phytohemagglutinin (PHA)-induced lymphoblastic transformation test. The response is compared with the immune response obtained in BALB/C mice of the corresponding age. The blastic transformation was significatively lower at 15, 25 and 35 weeks in the AKR/J mouse than in the BALB/C mouse. At the age of 45 weeks the AKR/J mouse shows an increased proportion of lymphocytes in the thymus and spleen, a weight increase of these organs, and an augmented lymphoblastic transformation in response to PHA. This phenomena are not observed in the BALB/C mouse. When macrophages are removed from the lymphocytes preparation, the PHA-induced blastic transformation of lymphocytes is not produced at any age in either AKR/J or BALB/C mice strains.

Aging↗