ABSTRACT
The effects of the platelet-activating factor (PAF) and the methoxy-PAF analog, 1-O-alkyl-2-methoxy-sn-glycero-3-phosphocholine, on platelet activation, oxidative burst in neutrophils and proliferation of K-562 and P815 cells have been studied. It has been found that the biological activity of methoxy-PAF for human platelets and neutrophils is commensurate with that of PAF. However, the cytotoxic properties of methoxy-PAF are much stronger than the cytotoxicity of PAF for tumour cells. It is concluded that the biological activity of methoxy-PAF is, to a great extent, due to its close structural resemblance to PAF as well as to the inability of cells to perform rapid metabolism of methoxy-PAF.
Subject(s)
Neutrophils/drug effects , Phosphatidylcholines/pharmacology , Platelet Activating Factor/pharmacology , Animals , Cell Survival/drug effects , Cells, Cultured , Decapodiformes , Humans , Mice , Neutrophils/metabolism , Tumor Cells, CulturedABSTRACT
The influence of the phospholipid platelet activation factor (PAF) was studied on pokeweed mitogen (PWM)-stimulated proliferation of peripheral blood lymphocytes in patients with bronchial asthma and normal subjects. It was found that PAF exerts dose-dependent activation with following suppression mainly on B-cells after its action on the whole population of lymphocytes activated by PWM. Besides, the influence of PAF on lymphocyte proliferation seemed to be mediated by monocytes since removal of monocytes from the whole population of mononuclear cells abolished the lymphocyte activation induced by PWM. Indomethacin inhibits lymphocyte proliferation activation induced by PAF. The results indicate that PAF has an effect on the IgE and IgG synthesis by blood B-lymphocytes in patients with bronchial asthma.
Subject(s)
Asthma/immunology , B-Lymphocytes/immunology , Lymphocyte Activation/drug effects , Platelet Activating Factor/pharmacology , Adult , B-Lymphocytes/cytology , Cell Division , Cells, Cultured , Female , Humans , Immunoglobulin E/biosynthesis , Immunoglobulin G/biosynthesis , Indomethacin/pharmacology , Male , Middle Aged , Pokeweed Mitogens/pharmacologyABSTRACT
The influence of the phospholipid platelet activation factor (PAF) was studied on PHA-stimulated proliferation of peripheral blood lymphocytes in patients with bronchial asthma and normal subjects. It was found that influencing on the whole population of lymphocytes PAF suppressed proliferation mainly of T-cells. Besides, the influence of PAF on lymphocyte proliferation seemed to be mediated by monocytes since removal of monocytes from the whole population of mononuclear cells abolished the suppression of lymphocyte proliferation induced by PHA. Pretreatment of lymphocytes with PAF antagonist--BL 8705 almost completely blocked the suppression of lymphocyte proliferation induced by PHA.
Subject(s)
Lymphocytes/drug effects , Platelet Activating Factor/pharmacology , Adult , Asthma/blood , Cell Division , Cells, Cultured , Female , Humans , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/drug effects , Lymphocytes/immunology , Male , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
The influence of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a platelet activating factor (PAF), and its structural analogs--1-acyl-2-acetyl-sn-glycero-3-phosphocholine and 1-(1'-alkenyl)-glycero-3-phosphocholine--on the histamine release from human leukocytes of healthy and allergic individuals was investigated. It was found that within the concentration range of 10(-10) to 10(-7) M PAF and its analogs induce a moderate histamine release from the leukocytes. However, at higher concentrations (greater than 10(-7) M) PAF induces an enhanced release of histamine from the leukocytes of allergic patients as compared to healthy individuals. PAF and its analogs significantly potentiate the allergens-induced release of histamine from the leukocytes of allergic patients. It was assumed that PAF induces the expression or demasking of additional numbers of IgE receptors on the surface of basophils, which leads tot he stimulation of histamine release from the leukocytes in the presence of allergens.