Leukocyte adherence inhibition test: cellular requirements for the elaboration of a polymorph adherence inhibition activity.
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Biomedical subjects
Publications and source records attributed to J Wybran.
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Lynestrenol, a synthetic progesteronelike drug, was assessed for its influence upon human leukocyte tests in vitro and in vivo. Lynestrenol markedly enhanced the lymphocyte response to phytohemagglutinin, the mixed lymphocyte culture, the active T-rosette test, the autologous red cell rosettes, and the number of nonadherent cells in the leukocyte adherence inhibition test. All these results indicate a stimulatory effect upon human T-cell function. Lynestrenol also increased monocyte phagocytosis. Lynestrenol delayed the appearance of malignant tumors in hamsters. Finally, lynestrenol, given to lung cancer patients, increased their T-cell functions as evaluated by skin tests. T-cell rosettes, and phytohemagglutinin response. Lynestrenol does possess immunostimulatory properties.
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This study reports the in vitro influence of morphine, dextromoramide, levomoramide, and methionine-enkephalin upon normal human T blood lymphocytes by using the active and total rosette tests. Morphine and dextromoramide inhibited the percentage of active T rosettes. This effect was completely reversed in the presence of naloxone, their specific antagonist. The specificity was further demonstrated by the absence of the effect of levomoramide, the inactive enantiomere, upon the rosette system. Methionine-enkephalin increased the percentage of active T rosettes. This effect was specifically inhibited by naloxone. These observations suggest that normal human blood T lymphocytes bear surface receptor-like structures for morphine, dextromoramide, and methionine-enkephalin. Such findings may provide a link between the central nervous system and the immune system.
Peripheral leucocytes from healthy blood-donors were preincubated in polyarthritic serum or normal serum and their adherence to glass tubes in the presence of synovial extract of control extract was measured. Serum from patients with inflammatory polyarthritis significantly reduced the proportion of leucocytes which adhered in the presence of synovial extract, but not control extract. Serum from patients with polyarthritis with visceral manifestations, patients with degenerative or metabolic polyarthritis or rheumatic fever, and controls did not have this effect. The leucocyte sensitising activity was eluted in the IgG fraction of serum, and could be absorbed by both synovial extract and IgG. It is thus probably IgG rheumatoid factor. In vivo, armed leucocytes in polyarthritic patients may bind to synovial tissue initiating or perpetuating the articular inflammatory process.
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The action of lynestrenol, a synthetic progesterone-like substance, was studied in Syrian golden hamsters inoculated with cells transformed by herpes simplex virus type I. Daily ip injections of 1 mg lynesterol/kg delayed tumor growth. Lynestrenol alone only slightly increased the survival of the animals. This effect was more marked when the animals were also given injections of Staphylococcus aureus Cowan A. Survivors showed an increased resistance to challenge with infected cells. Hamsters previously given injections of killed transformed cells and then challenged with living cells showed a facilitation of tumor growth. This facilitation was inhibited by lynestrenol alone or combined with S. aureus Cowan A.
This paper briefly reviews some mechanisms of tumor immunity and the principles of cancer immunotherapy. Cellular and humoral immunity can both influence tumor cells. Most of the cells belonging to the immune system can act on neoplastic cells. T cells can kill them, macrophages inhibit their growth, and K cells through their Fc receptor also destroy antibody-coated tumor cells. Cancer patients have usually depressed cellular immune functions. The goal of immunotherapy is to amplify the immune reactions in order to destroy the tumor cells. The modalities of immunotherapy are described. They may become important as adjuvant therapy. Immunotherapy has already been successfully in skin cancers, lung cancer and acute myeloblastic leukemia.
A woman with a T cell lymphoproliferative malignacy and heterozhgosity at the X chromosome-linked locus for glucose-6-phosphate dehydrogenase (G-6PD) isoenzymes was studied to find the clonal origin of her circulating neoplastic T cells. The red blood cells, polymorphonuclear cells, whole mononuclear cells, and T cell-depleted mononuclear cells contained both A and B isoenzymes of G-6-PD. In contrast, the tumor cells, separated by using their capacity to form rosettes with sheep red blood cells, contained only the B isoenzyme of G-6-PD. This observation strongly suggests the monoclonality of this T cell malignancy.
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The immune system is reviewed. Its ontogeny, differentiation and localization are discussed. Although cellular immunity mainly depends on T cells (thymus-derived) and humoral immunity depends on B cells (bone-marrow-derived), there are many interactions between these two systems. The role of T cells, in the production of antibodies, appears to be mainly regulatory. Various subpopulations of T cells are mentioned. The interactions between B cells and macrophages are described, as well as the markers of human T and B cells.
The influence of inosiplex upon various in vitro leucocyte assays was studied in normal individuals. It was found that the drug increases the response of bidirectional and unidirectional mixed lymphocyte cultures at concentrations of 200, 300, and 500 microgram/ml. It also significantly increases the percentage of active T rosettes (concentration range: 50 to 500 microgram/ml) and the percentage of autologous red cell T rosettes (concentration: 100 microgram/ml). In contrast, inosiplex did not modify the percentage of total T rosettes and EAC rosettes. Inosiplex increases the number of nonadherent leucocytes in the leucocyte adherence inhibition test at a concentration range between 100 and 300 microgram/ml. Finally, inosiplex also increases the percentage of monocytes phagocytizing yeast at a concentration between 50 and 500 microgram/ml. These data indicate that inosiplex enhances the function of normal human T cells, monocytes, and possibly neutrophils. Therefore inosiplex appears to have immunostimulant properties.
Lynestrenol, a synthetic steroid progesterone-like substance, has been found to enhance the stimulation of normal human lymphocytes. It increases the phytohemagglutinin response and the mixed-lymphocyte cultures. This augmentation can, in some cases, be higher than 100% of the phytohemagglutinin or mixed lymphocyte reaction baseline. There is no significant effect on the pokeweed mitogen stimulation. It is concluded that lynestrenol can modulate, "in vitro", some T cell functions.