Activation of human neutrophils by electronically transmitted phorbol-myristate acetate.

We report the transfer of the activity of 4-phorbol-12-beta-myristate-13-acetate (PMA) by electronic means. Neutrophils were placed at 37 degrees C on one coil attached to an oscillator, while PMA was placed on another coil at room temperature. The oscillator was then turned on for 15 min, after which cells were usually further incubated for up to 45 min at 37 degrees C before measurement of reactive oxygen metabolites (ROMs) production. In 20 blind experiments, PMA thus 'transmitted' induced ROM production. ROM were not induced when: (1) PMA vehicle or 4-alpha-phorbol 12,13-didecanoate (an inactive PMA analogue) were transmitted; (2) the oscillator was switched off; (3) superoxide dismutase or protein kinase C inhibitors were added to cells before transmission. These results suggest that PMA molecules emit signals that can be transferred to neutrophils by artificial physical means in a manner that seems specific to the source molecules.

Effect of Avène spring water on the activation of rat mast cell by substance P or antigen.

The biological activity of Avène water from two different springs ('Sainte Odile' and 'Val d'Orb') was studied in vitro on rat peritoneal mast cell activation. A dilution-dependent inhibition of both histamine and prostaglandin D2 antigen-induced release was observed when cells were preincubated with both Avène spring waters. They also inhibited histamine release triggered by substance P. The ability of Avène water to inhibit mast cell activation in vitro may be related with its antiallergic and anti-inflammatory properties and its use in hydrotherapy.

Decrease of ciliary beat frequency by platelet activating factor: protective effect of ketotifen.

The ciliary beat frequency (CBF) of the tracheal epithelial cells controls in part the respiratory tract mucociliary transport efficiency. We investigated the effects on CBF of PAF-acether (PAF) and its metabolite/precursor lyso-PAF. Guinea-pig tracheal rings were incubated for 3 to 6h with 1 microM PAF (C16, C18, C16/C18: 80/20%), lyso-PAF C16 or lyso-phosphatidylcholine (LPC). CBF changes were assessed by microphotooscillography (mean number of measures per ring = 14). We also examined the effect on PAF-induced CBF changes of the PAF receptor-antagonist WEB 2086, the anti-asthmatic/anti-anaphylactic drug ketotifen and the anti-histamine H1 pyribenzamine. CBF of control rings exposed to vehicle only from 0 to 6h showed no significant statistical variations (hertz, mean +/- SEM): 10.8 +/- 0.1 (n of measures = 890). By contrast, 1 microM C16, C18, and C16/C18 PAF significantly inhibited CBF after 3 to 6h incubation. C16 and C16/C18 PAF were more potent than C18 PAF (8.8 +/- 0.2, n = 112, 8.7 +/- 0.2, n = 64, and 9.6 +/- 0.1, n = 537 respectively; ANOVA analysis, p < 0.001 from control). At the same concentration, lyso-PAF also inhibited CBF, 9.5 +/- 0.1 (n = 197, p < 0.001) but not LPC, 10.5 +/- 0.2 (n = 127). WEB 2086 inhibited lyso-PAF and C16/18 PAF-induced CBF decrease. Preincubation (20 min) with ketotifen but not with pyribenzamine (1 microM) also suppressed the CBF inhibitory effect of PAF and lyso-PAF. Incubation of [3H]PAF with tracheal rings from 10 min to 6h resulted in its partial metabolism (25%) into [3H]lyso-PAF and a compound with a short retention time (10 min). [3H]lyso-PAF incubated for 3h with tracheal rings was partially metabolized (10%) into [3H]PAF and a compound with a short retention time. The PAF-induced decrease of CBF is congruent with its influence on pulmonary clearance, possibly via a specific receptor, since WEB 2086 abolished the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen may contribute to the therapeutic properties of this antiallergic drug.