leukotriene-b4 and Lymphoma

Topics: Antineoplastic Combined Chemotherapy Protocols; Epirubicin; Etoposide; Humans; Ifosfamide; Interleukin-3; Leukocyte Count; Leukotriene B4; Leukotrienes; Lymphoma; Recombinant Proteins

Chemotaxis is an essential physiological process, often harnessed by tumors for metastasis. CXCR4, its ligand CXCL12 and the atypical receptor ACKR3 are overexpressed in many human cancers. Interfering with this axis by

Topics: Cell Movement; Chemokine CXCL12; Humans; Leukotriene B4; Lymphocytes; Lymphoma; Receptors, CXCR; Receptors, CXCR4; Signal Transduction

Intravenous and orally administered beta-glucans promote tumor regression and survival by priming granulocyte and macrophage C receptor 3 (CR3, iC3bR and CD11b/CD18) to trigger the cytotoxicity of tumor cells opsonized with iC3b via anti-tumor Abs. Despite evidence for priming of macrophage CR3 by oral beta-glucan in vivo, the current study in C57BL/6 and BALB/c mice showed that granulocytes were the essential killer cells in mAb- and oral beta-glucan-mediated tumor regression, because responses were absent in granulocyte-depleted mice. Among granulocytes, neutrophils were the major effector cells, because tumor regression did not occur when C5a-dependent chemotaxis was blocked with a C5aR antagonist, whereas tumor regression was normal in C3aR(-/-) mice. Neutrophil recruitment by C5a in vivo required amplification via leukotriene B(4), because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B(4)R-deficient (BLT-1(-/-)) mice.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal; beta-Glucans; Cell Line, Tumor; Chemotaxis, Leukocyte; Complement C3a; Complement C5a; Granulocytes; Killer Cells, Natural; Leukotriene B4; Lymphoma; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Receptors, Leukotriene B4

Glucocorticoid-sensitive murine S49.1 lymphoma cells respond in a biphasic way to the steroid challenge. The first effect of corticosteroids is to induce a reversible growth inhibition, which is probably permissive for the following cytolysis. Distinct mechanisms for the two effects are likely. Since dilution of S49.1 lymphoma cultures resulted in a drastic reduction of the proliferation rate, which could be overcome by the addition of conditioned medium, the proliferation appears to depend on the presence of autocrine growth factors. Therefore, the cytostatic effect of corticosteroids could possibly be attributable to an interference with the production of endogenous growth factors. Analysis of the growth-promoting activity in culture supernatant showed that the critical growth factor in diluted cultures is an arachidonic acid metabolite, the leukotriene B4. The role of leukotriene B4 in S49.1 cell proliferation received further support from the finding that while nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway which is necessary for leukotriene formation blocked lymphoma multiplication, indomethacin, an inhibitor of cyclooxygenase activity, did not affect proliferation. Quantitation of the leukotriene B4 content of dexamethasone-treated vs. untreated cultures revealed an almost complete inhibition of leukotriene production, pointing to the significance of this mechanism for the glucocorticoid-induced lymphoma growth inhibition. Moreover, these findings offer a new approach to increase the therapeutic effectiveness of glucocorticoid therapy of steroid-sensitive leukemias and lymphomas.

Topics: Animals; Cell Division; Cell Survival; Dexamethasone; Glucocorticoids; Indomethacin; Interphase; Leukotriene B4; Lipoxygenase Inhibitors; Lymphoma; Masoprocol; Mice; Tumor Cells, Cultured

Peripheral blood neutrophils and eosinophils from 70 patients and controls were studied for their in vitro chemotactic and chemokinetic responses towards synthetic leukotriene B4 (LTB4), 20-OH-LTB4 and 20-COOH-LTB4. All three factors induced chemotaxis and chemokinesis of cells. 20-OH-LTB4 was always less and 20-COOH-LTB4 even less active than the parent compound. Cells from patients with atopic eczema and T cell lymphoma moved less than cells from normal controls or from patients with psoriasis. In the presence of LTB4, 20-OH-LTB4 and buffer alone, more eosinophils than neutrophils moved to the lower side of the filter, while this did not occur with platelet activating factor as chemoattractant. Studies of neutrophil and eosinophil chemotaxis in the presence of LTB4 should therefore always take into account a high variability of the quantitative response which is donor and disease dependent.

Topics: Chemotaxis, Leukocyte; Dermatitis, Atopic; Eosinophilia; Eosinophils; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lymphoma; Neutrophils; Psoriasis