Increased percentage of activated T lymphocytes in B cell lymphocytic leukaemia (B-CLL) patients.
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The chemokinetic inhibitory factor (CIF) is a recently described B-cell derived lymphokine that mediates a chemokinetic inhibitory effect on human polymorphonuclear leukocyte (PMN) migration. In the present report the interaction of CIF with the neutrophil plasma membrane was studied. Normal human peripheral blood neutrophils and purified neutrophil plasma membranes selectively removed biologic activity from CIF-containing concentrates obtained during the purification procedure from conditioned medium. Removal was obtained at both 4 degrees C and 37 degrees C. Furthermore, HL-60 cells treated with dimethyl sulfoxide removed CIF activity (granulocyte-like cells) but HL-60 cells treated with 12-O-tetradecanoylphorbol-13-acetate (macrophage-like cells) did not. Purified human blood monocytes, cells from the macrophage-like U-937 cell line and cells from the basophilic leukemia cell line KU-812 did not remove CIF. These studies suggest that neutrophils express specific binding sites for CIF-activity.
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Malignant B-1 cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for the expansion of malignant B-1 cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-1 cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-1 malignant clones. In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically. IL-10 may enhance proliferation and the development of B-1 cell malignancy rather than antibody production by the B-1 cell subpopulation. Thus, IL-10 plays an important role in B-1 malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies.
The authors studied the behavior of some enzymes involved in purine nucleotide metabolism in human peripheral blood lymphocytes from normal and B-cell chronic lymphocytic leukemia subjects. Determinations were made with radiochemical methods associated with high performance liquid chromatography. Results indicated a marked increase in de novo purine synthesis enzymes, particularly those of the "inosinic branch point". The latter were absent in normal lymphocytes, whereas they were well evident in leukemic lymphocytes, with the exception of AMP-S synthetase. Whereas the enzymes of the "salvage pathway" were spared in comparison to other proteins, those of the "catabolic pathway" significantly decreased. The authors discuss the possibility that such enzymes may be used as tumor markers.
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