Biomedical subjects
Publications and source records attributed to W Leibold.
Following a short overview of anatomical distribution pattern and functions of neutrophils diagnostic methods of evaluating their different functions are summarized. Therapeutic uses for granulocyte-colony-stimulating factor are discussed.
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The determination of differentiation and transplantation antigens will be of growing importance in immune diagnosis for individual animals as well as for breeding purposes in populations. Differentiation antigens characterize subsets of cell populations and indicate their functional capacity while transplantation antigens represent markers of individuals of a species. Occurrence and significance of these antigenic systems are briefly reviewed.
Calves were treated with different doses of lead acetate to investigate the influence of chronic subclinical lead intoxication on the immune system. A seven months old heifer fell ill showing typical signs of acute lead intoxication. This animal had been fed 0.316 mg lead for three months and 5 mg Pb/kg body weight/day for 17 days afterwards. Following symptoms were observed: Derangement of the central nervous system, paresis of the left body side, motor paralysis of the chewing muscles and disturbances of swallowing activity. Furthermore tooth grinding and attempts to push against, or climb walls were seen. After a single dose (2g) Ca-EDTA the heifer recovered progressively in 18 days.
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A high molecular polyanion, Liquoid, was found to inhibit at nontoxic concentrations (12-50 micrograms/ml) the natural killing (NK) and the antibody-dependent cellular cytotoxic (ADCC) activity of human peripheral blood mononuclear cells selectively. Whereas NK of the K 562 target cell was slightly or not at all affected, the spontaneous lysis of PDe-B-1, an EBV-transformed B-cell line, was strongly inhibited or even completely abolished. ADCC activity could only be inhibited by Liquoid if the target cells were mycoplasma-free, while the polyanion had no effect when mycoplasma-contaminated target cells were used. Liquoid did not alter the target binding capacity of the NK effector cells and did not activate monocytes or induce other suppressive cells. Alpha interferon, but neither beta nor gamma interferon, was able to neutralize the NK reduction. These results suggest that Liquoid inhibits a target cell-related, selective process in the post-binding stage of NK cell lysis.
The influence of therapeutic dosages of factor VIII, factor IX and immunoglobulin preparations on the proliferative capacity of mitogen-activated lymphocytes from patients with hemophilia or idiopathic thrombocytopenia was investigated. Addition of protein preparations in vitro led to inhibition of lymphocyte proliferation, predominantly with the mitogen staphylococcus enterotoxin B. After intravenous application of proteins also stimulatory effects were seen. Since long-term treatment with protein preparations might impair immune functions, their application should be considered carefully.
In vitro resting, short-term mitogen stimulated, and proliferating rat thymocytes as well as established human T and B lymphoblastoid cell lines were compared in their capacity to metabolize glucose and glutamine as energy source. Furthermore, the pathways of glutamine metabolism in these cells were studied. Compared with resting thymocytes, glucose metabolism of proliferating thymocytes was 36-fold increased during the incubation; 92% of the amount of glucose utilized was converted into trioses mainly lactate, whereas resting cells metabolized only 38% to trioses. However, the latter oxidized 19% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Rates of glucose uptake and degradation to products by the malignant T lymphoblastoid cell line (Jurkat) were nearly identical with those observed with proliferating rat thymocytes, whereas the benign B lymphoblastoid cell lines (DHg-B-1 and LV-B-1) showed significantly higher rates of glucose metabolism. All three transformed lymphoblastoid cell lines, however, metabolized glucose almost completely to lactate as did the proliferating rat thymocytes. Lymphocytes are able to utilize glutamine with glutamate, aspartate and ammonia being the major end-products. A complete recovery of glutamine carbon in the products was obtained with all cells. Glutamine utilization by incubated proliferating rat thymocytes was 8-fold increased as compared to the resting cells. Again the human T lymphoblastoid cell line showed the same rates of glutamine uptake and conversion into products as did the proliferating rat thymocytes, whereas both B lymphoblastoid cell lines had about 2.5-fold enhanced rates as compared to the T cell line. The results indicate that during lymphocyte proliferation caused by mitogen stimulation as well as by permanent transformation into lymphoblastoid cell lines glucose metabolism is altered not only quantitatively but also qualitatively by changing from partly aerobic to almost complete anaerobic glucose breakdown. Glutamine has been found to be a suitable energy source for lymphocytes. About 75% of the amount of glutamate derived from glutamine entered into the citric acid cycle via the aspartate aminotransferase, and the remaining 25% via the glutamate dehydrogenase reaction. The changes in metabolic rates observed in proliferating as well as in transformed or leukemic lymphocytes appear to be reliable parameters to characterize the state of lymphocyte activation or to evaluate the efficacy of lymphokines.
The content and relative biosynthetic rates of thymosin beta 4 have been determined in 28 different cell lines. The highest content of thymosin beta 4 as well as the highest rate of biosynthesis was observed in Epstein-Barr virus-transformed human B-cell lines. The levels observed in these cells are 1 pg thymosin beta 4 per cell, which is three times higher than that in rat peritoneal macrophages. Thus, these B-cell lines have the highest content of thymosin beta 4 of any cell type yet described. Since all of the Epstein-Barr virus-transformed B-cells described here grow in suspension, it is unlikely that the presence of thymosin beta 4 is related to anchorage in these cells. Thymosin beta 4 is not secreted by viable Epstein-Barr virus-transformed B cells in culture, suggesting some intracellular function of the peptide. These results indicate that these B-cell lines may be suitable for the study of thymosin beta 4 function.
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Peripheral blood mononuclear cells from patients with multiple myeloma, gastrointestinal tumors, and inflammatory bowel disease were analyzed for binding of various lectins. The results demonstrated that in most of the patients with multiple myeloma a significantly increased percentage of cells positive for Lotus tetragonolobus agglutinin (LTA), peanut agglutinin (PNA), soybean agglutinin (SBA), and wheat germ agglutinin (WGA), and a decreased number of Agaricus bisporus agglutinin (ABA) positive cells were present as compared to a normal control group. This could not be shown in malignant or inflammatory disorders of the gastrointestinal tract where only some patients exhibited an increased PNA and LTA binding, respectively. Patients with the systemic malignant disease differed from patients with solid localized tumors by a significantly altered number of ABA, LTA and SBA-positive peripheral blood mononuclear cells. Double fluorescence studies using monoclonal antibodies and lectins revealed that most of the cells expressing receptors for ABA had also receptors for OKT3, whereas most of the cells with receptors for LTA, PNA, SBA, and WGA were found to be positive for OKM.
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The aim of this study was to define the significance of HLA-DR+ cells for the in vitro induction of human autoreactive T cell proliferation. Proliferation was induced by autologous or allogeneic non-T cells or EB virus-transformed LCL. Pretreatment of stimulator cells with low concentrations of RAHLA-DR and C and with high amounts of RAHLA-DR alone abolished the capacity to stimulate autologous or allogeneic T cells. This suggested that antigens associated with HLA-DR+ stimulator cells or HLA-DR itself are involved in the induction of this proliferation. At the responder cell level the cytotoxic elimination of HLA-DR+ cells as well as depletion of adherent cells by passage through Sephadex G-10 columns reduced both autoreactive and alloreactive responsiveness. Responses of serologically and physically depleted populations were both restored by reconstitution with mitomycin-C treated autologous adherent cells. These cells were resistant to lysis with T cell specific antibodies and preferentially cooperated with T cells of autologous deprivation. Co-cultivation experiments further revealed that such accessory cells were capable of amplifying T cell proliferation in the presence of suboptimal numbers of autologous LCL. We concluded, therefore, that an HLA-DR+-adherent cell, presumably of monocytic origin, is required for optimal proliferative responsiveness of both autoreactive and alloreactive T cells.
Cleaning of human tumor cell lines from arginine-dependent nonfermentative Mycoplasma orale 1 (MO1) by a recently developed technique profoundly altered several in vitro properties of the cell lines. Four melanoma lines (Mel I, Mel St, Mel K, IGR3) and 1 ovarian carcinoma line (Ro) induced human leukocyte interferon (IFN-alpha) only in the mycoplasma-infected state and not in the mycoplasma-free state. MO1-infected tumor lines were generally more susceptible to natural killer (NK) cell-mediated lysis than their mycoplasma-free counterparts. Reinfection of cleaned tumor lines with MO1 restored their interferonogenicity and the increased susceptibility to NK lysis. Thus, the amplifying role of MO1 infection on NK target lysis occurred in connection with an increased production IFN-alpha during the assay period. The human erythroleukemia cell line K562 was exceptional in that it also induced high levels of IFN in an apparently mycoplasma-free state and was unaffected in its susceptibility ot NK lysis by infection with MO1. Possible implications of these findings for the biologic significance of the NK reaction are discussed.