ABSTRACT
The pro- and anti-inflammatory activity of new structural analogues of the platelet-activating factor (PAF) was studied. It was found that three PAF analogues inhibit PAF-induced rat paw edema in a dose-dependent manner. The anti-inflammatory activity of one of the PAF analogues upon PAF- or carrageenan-induced inflammation was comparable or in some extent exceeded that of dexamethasone.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Platelet Activating Factor/analogs & derivatives , Platelet Activating Factor/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Aspirin/therapeutic use , Carrageenan , Dexamethasone/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Indomethacin/therapeutic use , Inflammation/chemically induced , Inflammation/drug therapy , Male , Rats , Rats, Inbred StrainsABSTRACT
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 cardiodepressive effect of PAF has been studied on the electrical and mechanical activities of isolated auricles of guinea pig. Intracellular resting potential, action potential (AP) and isometric contractions elicited by electrical stimulation (0.5 Hz) were measured. PAF (10(-7) M) induced negative inotropic effect, which reached its peak after 5 min with 23.5 +/- 6.6% in respect to prechallenge values (n = 8). After 20 min negative inotropic effect relaxed to 39.6 +/- 8.8%. 1 min after the beginning of washing in Tyrode solution, positive inotropic effect of PAF was evident, that reached its peak (217 +/- 49.5%) after 2 min, decayed after 5-10 min to normal values. PAF did not modify the resting membrane potential, produced a decrease in the amplitude and Vmax of the upstroke AP, shortened the AP duration. Ca-AP and contractions, elicited in partially depolarized myocardium were decreased by PAF (10(-7) M). PAF-produce the change of the AP and the negative effect on auricle contractile force was inhibited in muscles pretreated with 3mM 4 aminopyridine. Histamine (10(-4) M) was also capable of neutralizing the depressant effect of PAF. The obtained results suggested that PAF effects on the membrane of cardiac cells could be related to a change in Ca and K conductance.