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M Zöller

Publications and source records attributed to M Zöller.

At least 145 records · Page 8Linked to original sources
PubMed1984

Natural cytotoxicity in lymphatic metastasis. I. In vitro studies using the rat tumor BSp73 and its variants.

Serial transplantation of primary BSp73 ascites cells to a subcutaneous (SC) site gave rise to the appearance of two solid variants differing in their capacity to metastasize via the lymphatics. Tissue cultures derived from variant AS (nonmetastasizing) showed epithelioid morphology, while cultures derived from variant ASML (metastatic) showed spherical morphology. Upon cloning, both variants proved to be operationally homogeneous. Susceptibility of cultured BSp73 cells to NK and macrophage-mediated cytotoxicity was closely correlated to morphology, inasmuch as epithelioid cells were susceptible, while spherical cells were resistant, to lysis. With stimulated effector cells a general increase in cytotoxicity was observed, but epithelioid cells still showed a higher susceptibility level. Resistance of ASML-type cells to natural cytotoxicity was not due to the lack of recognition structures or to a general increase in the mechanical stability of spherical cells. This was concluded from cold target inhibition and from hypotonic shock treatment experiments, respectively.

Animals↗
PubMed1984

Comparison between the in vitro activities of in vivo-induced hapten-specific suppressor cells and supernatants of a hapten-specific suppressor hybridoma.

A trinitrophenyl (TNP)-specific suppressor hybridoma was obtained by fusing hapten-binding spleen cells (SC) of BALB/c mice 1 week after intravenous (iv) injection of TNP-modified syngeneic lymphocytes with the AKR lymphoma BW5147. The suppressive activity of supernatants from one clone (TNP-44) was compared with that of in vivo-induced TNP-specific suppressor cells. Both the TNP-specific suppressor cells (TsTNP) and the TNP-44 were hapten binding and hapten specific. They suppressed the functional activity of TNP-haptenized T as well as B cells. TNP-44 supernatant also inhibited the proliferation of TNP-modified cells. Using native target cells, both TNP-44 supernatant and the in vivo-induced suppressor cells suppressed the anti-TNP B-cell response to TNP-bound T-dependent soluble or cellular antigens, but not to TNP-lipopolysaccharide (LPS). Furthermore, the function of TNP-specific helper T cells (THTNP) was impaired in the presence of TSTNP or supernatant from TNP-44. From these observations it was concluded that both the TSTNP and a TNP-specific factor derived from a suppressor hybridoma function via an antigen bridge at the TH or at the TH-dependent B-cell subset.

Animals↗
PubMed1984

Comparison between Nu/Nu and normal BALB/c T-helper activity in anti-hapten and anti-carrier responses.

Nu/nu BALB/c mount a primary in vivo anti-TNP response to T-dependent TNP-antigens in the range of normal BALB/c mice. However, the response against the carrier (horse red blood cells, HRBC) was in the magnitude of about 5% as compared to normal BALB/c mice. Neither against the hapten, nor against the carrier a secondary response was observed. It could be shown by in vitro experiments that nu/nu contain a small population of TNP specific as well as HRBC specific T-helper (THTNP, THHRBC) cells. But even within the small nu/nu T-cell population, TH cells are less frequent than in T-cell populations of normal mice. Furthermore, the difference in help between nu/nu and normal BALB/c was more pronounced with respect to the anti-HRBC than the anti-TNP response. These observations could explain the lack of a secondary in vivo response being due to the low number of TH cells and the apparent in vivo unresponsiveness against HRBC as a consequence of the low frequency of THHRBC.

Animals↗
PubMed1984

Concomitant induction and persistence of hapten-specific suppressor and helper T cells in vivo.

Intravenous injection of haptenized syngeneic lymphoid cells in the mouse induced a suppression in vivo against any immunogen carrying this hapten, introduced as a second antigen. Suppression was observed against any epitope on such a haptenized immunogen, thus largely excluding cross-reactions at the level of antigen-binding or idiotypy. However, when cells from such suppressed mice were assessed in vitro, it could be shown that significant T-helper activity had been induced by the same procedure, which in vivo resulted in suppression only. Thus, concomitant induction and persistence of hapten-specific suppressor and helper T cells is a result of the present immunization protocol. Both phenomena express the conventional requirements for physical linkage between hapten and immunogen to have an impact on the antibody response against the epitopes of the carrier. It is thus likely that the observed suppression/help in the present system does function at the level of handling the intact immunogen.

Animals↗
PubMed1984

[Antidepressive effect of a Hypericum extract standardized to an active hypericine complex. Biochemical and clinical studies].

In 6 women with depressive symptoms aged 55-65 years the effect on the excretion of urinary metabolits of noradrenaline and dopamine was measured after a monotherapy with the active hypericine complex (Psychotonin M). In all patients there was a significant increase in 3-methoxy-4-hydroxyphenylglucol which is considered an expression of a beginning antidepressive reaction. With the same patients supplemented with further 9 cases the clinical influence on the depression was measured during a period of 4-6 weeks, with the rating-scales SCAG (Clinical assessment geriatric scale) and DSI (Depression Status Inventory) there was shown a quantitative improvement of the items anxiety, dysphoric mood, loss of interest, hypersomnia, anorexia, depression regularly worse in the morning, insomnia, obstipation, psychomotoric retardation and feeling of worthlessness.

Adult↗
PubMed1983

Natural killer (NK) cells in the rat: "heterogeneity" as reflection of the activation status.

Rat natural killer (NK)/natural cytotoxic (NC) cell activity was tested in a 4-h and a 20-h 51-Cr-release assay. In the 4-h assay, NK activity was high with peritoneal cells (PC), medium with peripheral blood lymphocytes (PBL) and spleen cells and low with bone marrow (BM), thymus and lymph node (LN) cells. The differences in lytic capacity were less pronounced in a 20-h assay. This led to the suggestion that NK/NC cells may get activated upon coculture with tumor cells during the long-term assay and that the short-term assay actually reflects the activation status of NK/NC cells in different organs rather than non-identity of cells with natural cytotoxic potential. This was supported by the following observations: 1. After in-vivo or in-vitro activation of NK cells, increased reactivity was observed in a 4-h assay especially with lymphoid cells of organs with low or medium NK activity and the differences to a priori highly active organs were significantly diminished. 2. Neither by biophysical (density) nor by biochemical (surface markers) methods differences between NK versus NC cells could be substantiated. 3. Closely related patterns of cytotoxicity were observed using adherently growing or lymphoid tumor target cells.

Animals↗
PubMed1983

Solid tumor-derived target cell susceptibility to macrophages and natural killer/natural cytotoxic cells in the rat.

Cytotoxic capacity of rat macrophages (M phi) and natural killer (NK)/natural cytotoxic cells (NC) against adherent growing, solid tumor-derived target cells was evaluated, modulating the activation status of effector cells and growth conditions of target cells. Testing a panel of target cells, cytotoxicity of NK/NC and M phi was strikingly correlated so that besides of target-cell binding structures basic lysability seems to be of influence with respect to cytotoxicity rates. Varying the in vivo growth conditions of target cells altered their lysability by M phi and NK/NC cells in the sense that ascitic versus subcutaneously (sc) grown tumors were more resistant to lysis. On the other hand, in vitro culturing did not influence susceptibility for M phi, but with some tumor lines increased lysis by NK/NC cells was observed. In the rat, the activation status of M phi and NC was not age-dependent, and NK cell activity only declined slowly with age. But cytotoxic potential of M phi obviously presents a strain characteristic, different from NK/NC cell activity, only the latter two correlating in different rat strains. Experiments to augment natural cytotoxic capacity revealed that application of Corynebacterium parvum (CP) activated M phi and NK/NC cells, while sc tumor implantation only resulted in increased NK/NC cell cytotoxicity, leaving M phi unaltered.

Animals↗
PubMed1983

Rat natural killer (NK) cells are not bone marrow dependent.

Rats were treated with various doses of 89Strontium. At a dose effecting depletion of the bone marrow (200 muCi), NK activity of spleen, peritoneal and peripheral blood lymphocytes was unaltered or only slightly decreased. At higher doses (400 muCi), a general impairment of the immune system, including T-cell functions, was observed. After application of 700 muCi 89Strontium, rats died within three weeks.

Animals↗
PubMed1983

Characterization of effector cells mediating IgG and IgM antibody-dependent cellular cytotoxicity.

Spleen effector cells for IgG- and IgM-induced antibody-dependent cellular cytotoxicity (ADCC) were characterized with respect to density and cell surface markers by using sheep erythrocytes (SRBC) coated with hybridoma-derived monoclonal anti-SRBC IgG or anti-SRBC IgM antibodies as targets. While basically the same effector cells are cytolytic for IgG and IgM antibody-coated SRBC, they differ with respect to their relative killing capacity for IgG- versus IgM-coated target cells. On the basis of physical and biochemical properties three populations with cytolytic capacity could be separated: (I) A light fraction of large cells had high cytolytic potential for both IgG- and IgM-coated SRBC. The cells were negative for the Fc receptor for IgG (Fc gamma-R-) and the C3-receptor (C3-R-), they carried the receptor for Helix pomatia A agglutinin (HP-A+), and reactivity was strongly reduced after treatment with anti-Thy-1 and complement (C). (II) High activity was also observed with a medium-dense fraction, preferably lysing IgG antibody-coated cells. The cells were Fc gamma-R+, partly C3-R+, mostly HP-A-, and only a minor portion of the cells were Thy-1+. (III) A dense fraction, displaying on a per cell basis low cytolytic potential, was more active in IgM than IgG ADCC. The cells were Fc gamma-R+, HP-A+ and Thy-1+. All three effector cell populations were non-adherent, non-phagocytic, and surface immunoglobulin-negative (s-Ig-).

Animals↗
PubMed1983

Postsurgical follow-up of colorectal cancer patients monitored by the leukocyte migration test.

Blood samples from more than 1,000 patients with colorectal cancer were tested in the leukocyte migration test (LMT) and by a radioimmunoassay for carcinoembryonic antigen (CEA) for evaluation of: 1) the correlation of LMT response to the status of disease and 2) the use of LMT and CEA determination in the monitoring of patients after surgical removal of the primary tumor. A total of 320 patients, which were tested repeatedly, constituted the key group of the investigation: Of these, 56 patients developed recurrences or metastases whereas 217 patients showed no sign of reactivated disease. The group of patients with persistent absence of disease showed test profiles of either persistent negativity (50%) or conversion of one or both parameters; persistently positive profiles were rarely encountered. Patients with recurrences and metastases showed either positive profiles or conversion of positivity; only 3 patients were negative in both tests. However, despite significant disease-related response of the LMT, the test is not recommended as an adjunct to postsurgical monitoring, because of its technical complexity.

Carcinoembryonic Antigen↗
PubMed1983

Characterization of BSp73, a spontaneous rat tumor and its in vivo selected variants showing different metastasizing capacities.

BSp73 arose spontaneously (1979) as intraperitoneal nodules together with ascites. Histologically, the nodules were classified as adenocarcinoma of the pancreas. During serial transplantation of ascites cells to a subcutaneous site, two variants appeared--one fast-growing, nonmetastasizing, the other slowly growing and metastasizing via the lymphatic system to the lung. From the in vivo selected variants as well as from the parental tumor, two types of tissue cultured cell lines were established. These differed in morphology, adherence to plastic, susceptibility to detachment by trypsin, and, above all, in the ability to metastasize upon reinjection into syngeneic recipients. From differences in growth kinetics in vivo it has to be concluded that variant cell types coexisted in the parental tumor in the form of precursors, which adopted their characteristic features (irreversibly) after a shift in the environment.

Animals↗
PubMed1982

Mechanisms of cellular cytotoxicity mediated by effector cells from rats with spontaneous tumors.

We have previously shown that effector cells from BD X rats bearing spontaneous tumors display increased cytotoxicity towards syngeneic tumor cells compared to effector cells from untreated rats (Zöller and Matzku, 1980 a). The increased in vitro cytotoxicity of lymphoid cells from tumor-bearing (TB) animals was not T-cell mediated and the question was raised, whether it was due solely to increased natural killer (NK) cell activity, or whether humoral factors could also be involved. We now prove that in a long-term assay, the presence of B cells is indeed mainly responsible for increased TB cytotoxicity, since: (1) After depletion of surface immunoglobulin positive cells (s-Ig+), TB cytotoxicity no longer exceeds cytotoxicity of effector cells from untreated rats; (2) Mixtures of s-Ig+ cells from TB animals with Fc-receptor positive (Fc-R+) cells from untreated rats restore the increased TB cytotoxicity; (3) Addition of rabbit Fab' anti rat F(ab')2 reduces TB-effector cell cytoxicity. A minor contribution of the increased TB cytotoxicity by activation/numerical increase of NK cells will be discussed.

Animals↗
PubMed1982

Natural and antibody-dependent killer cells in the thymus.

Thymocytes contain a small population of light (o = 1.067), large cells with high cytolytic potential against natural killer target as well as against IgG- or IgM-coated erythrocytes and nucleated cells, thus displaying natural killer and antibody-dependent cellular cytotoxicity functions, but not exhibiting T killer cell capacity. As far as characterized, the cells show T cell characteristics: they are nonadherent, nonphagocytic, surface immunoglobulin-negative, C3 receptor-negative, partly Fc gamma receptor-positive, carry the receptor for Helix pomatia A agglutinin, and are, at least partly, cortisone-resistant and Thy-1-positive. The implications of this finding with respect to the lineage of natural killer and killer cells and their interdependence will be discussed briefly.

Animals↗
PubMed1982

Rat macrophages inhibit natural killer (NK) cell activity against adherent growing target cells.

Peritoneal as well as peripheral blood, but not spleen macrophages inhibit natural killer (NK) cell activity directed against adherent growing target cells. Inhibition was observed with macrophages (Mø): spleen cell ratios as low as 0.01:1. It was independent from the activation status of Mø and was not MHC restricted. With respect to the mechanism, cell contact was essential. A cold target mechanism, reflected by some binding, but not killing, of NK cells by Mø was of minor influence. Spontaneously by Mø released soluble mediators could be excluded, nor was any soluble mediator released upon contact of Mø with spleen cells, but NK activity could be partly inhibited by supernatants from cocultures of Mø with adherent growing target cells.

Animals↗
PubMed1982

Natural killer cells do not belong to the recirculating lymphocyte population.

Natural Killer (NK) cells constitute a cell type with an as yet undefined lineage, although certain similarities with T lymphocytes have been found in the mouse. Our present results show that NK cells have a significant difference compared with T and B cells in their capacity to traverse the blood-lymph barrier. Thoracic duct lymphocytes from mice or rats are thus devoid of NK activity, when at the same time potential, cytotoxic T lymphocyte (CTL) activity or antibody-dependent cellular cytotoxicity function can be demonstrated. Chronic thoracic duct drainage in the rat also leads to an increase in NK activity per unit cell number in the other lymphoid organs. Thoracic duct lymphocytes from mice and rats may thus serve as convenient sources of CTL and/or killer cells in situations in which it is important to minimize NK cell involvement.

Animals↗