Potentiation of Histamine Release from Human Leucocytes by Paf

in Agents and Actions (1994), 41(1-2), 5-10

Studies on the effects of PAF on histamine release from human leucocytes have yielded conflicting results. We therefore investigated the effects of PAF on leucocytic histamine release (HR) focusing on ... [more ▼]

Studies on the effects of PAF on histamine release from human leucocytes have yielded conflicting results. We therefore investigated the effects of PAF on leucocytic histamine release (HR) focusing on direct as well as on modulating effects. Peripheral blood leucocytes of normal and atopic subjects were incubated with PAF, anti-IgE and FMP for 30 min at 37 degrees C, and histamine was measured fluorometrically. Unlike anti-IgE (1/2000) and FMP (10(-5) M) which caused histamine release (HR) of 34 +/- 7% and 31 +/- 8%, respectively, PAF by itself (10(-11)-10(-5) M) failed to induce any significant HR from human leucocytes (< 3%) in normal (n = 14) and atopic subjects (n = 6). Nevertheless, in normals as well as atopics, PAF, but not lyso-PAF, enhanced anti-IgE (1/2000) and FMP (10(-5) M)-induced HR in a concentration-related manner. Maximal potentiation of histamine release caused by FMP and anti-IgE was achieved with PAF (10(-7)) (mean +/- SEM: 26 +/- 5%, n = 5, p < 0.01) and PAF (10(-5)) (mean +/- SEM: 20 +/- 7%, n = 7, p < 0.05), respectively. This potentiation was suppressed by WEB2086 (10(-5) M), a specific PAF antagonist. The time course of the enhancing effect produced by PAF was dependent on the type of secretagogue. The enhancement was nearly maximal when PAF and FMP were added simultaneously to the leucocytes, whereas a preincubation of 20 min with PAF was required to get maximal enhancement with anti-IgE. The enhancing activity of PAF on HR induced by both anti-IgE and FMP was reversed by washing the cells after preincubation. While PAF enhancement of FMP-induced HR persisted on mononuclear cell fraction containing basophils, that of anti-IgE-induced HR was considerably reduced under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Plasma Histamine and Bronchial Reactivity in Allergic Asthma

in Allergy (1993), 48(7), 547-9

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic ... [more ▼]

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic asthmatic patients have yielded controversial results. We therefore measured plasma histamine and bronchial reactivity in 30 nonsmoker volunteers taking no medication. Eleven were normal subjects; 19 were stable, mildly allergic asthmatic patients. Venous blood was taken to measure blood cells and basal plasma histamine by radioimmunoassay. After blood sampling, all subjects underwent a measurement of PC20M (concentration of methacholine causing a 20% fall in FEV1). Mean plasma histamine levels were 0.21 +/- 0.1 ng/ml and 0.44 +/- 0.3 ng/ml in normal and asthmatic subjects, respectively (P < 0.05). We found a significant increase of blood eosinophils and basophils in asthmatic patients, and a positive correlation between plasma histamine and circulating basophils. PC20M was greater than 16 mg in normal volunteers, and mean PC20M was 2.1 +/- 2 mg/ml in asthmatic patients. PC20M did not correlate with plasma histamine levels, but it did so negatively with blood eosinophils. The increased plasma histamine concentration in mildly atopic asthmatic patients might be a consequence of the high basophil releasability of atopics and the higher basophil counts in allergic asthma. Plasma histamine is thus unlikely to be a determinant of BHR in asthma. [less ▲]

No Increase in Plasma Histamine During Paf-Induced Airway Obstruction in Allergic Asthmatics

in CHEST (1993), 104(3), 806-10

To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single ... [more ▼]

To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single dose) on plasma histamine, bronchial caliber, and leukocyte and platelet counts in six patients with mild or moderate allergic asthma (mean age, 27 +/- 1.3 years; mean FEV1, 95 +/- 5 percent of predicted; mean PC20 methacholine, 1.46 +/- 0.36 mg/ml). Specific conductance (SGaw) FEV1, FEF25-75 percent, differential leukocyte and platelet counts, and plasma histamine (radioimmunoassay) were measured before and 5, 10, 15, and 20 min after PAF inhalation. Mean basal plasma histamine level was 0.28 +/- 0.04 ng/ml. Inhalation of PAF caused a fall in SGaw peaking at 5 min (43 +/- 9 percent) and a fall in FEV1 and FEF25-75 peaking at 10 min (19 +/- 10 percent and 30 +/- 13 percent, respectively). There was also a rapid and transient fall in circulating neutrophils at 5 min (from 3,096 +/- 204/mm3 to 2,551 +/- 158/mm3, p < 0.05) followed by a rebound neutrophilia. In contrast, plasma histamine level did not change significantly at any time measured. Conversely in the same asthmatics, a rapid rise in plasma histamine level (from 0.29 +/- 0.03 ng/ml at baseline to 0.53 +/- 0.06 ng/ml at 5 min; p < 0.01) was observed after an allergenic challenge (Dermatophagoides pteronyssinus) causing a fall in FEV1 peaking at 10 min (22 +/- 4 percent). Thus, inhaled PAF may induce airway obstruction and neutropenia in asthmatics without any significant change of plasma histamine level. These results indicate that it is unlikely that lung mast cells or basophils degranulate during PAF-induced bronchoconstriction. [less ▲]

Chylothorax: a rare complication of endoscopic variceal sclerotherapy.

in European Journal of Gastroenterology & Hepatology (1993), 5

Ly 186655, a Phosphodiesterase Inhibitor, Inhibits Histamine Release from Human Basophils, Lung and Skin Fragments

in International Journal of Immunopharmacology (1992), 14(2), 191-4

LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived from the xanthine, possessing bronchodilating activity in animals. The aim of this work was to study the effect of LY 186655 ... [more ▼]

LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived from the xanthine, possessing bronchodilating activity in animals. The aim of this work was to study the effect of LY 186655 and theophylline on histamine release from human leukocytes, skin and lung fragments. Histamine was measured using a spectrofluorometric method. Both drugs (3 x 10(-5)-3 x 10(-3) M) exhibited a dose-dependent inhibition on anti-IgE (1/2000)-induced histamine release from human leukocytes. At 3 x 10(-3) M, theophylline was significantly more effective than LY 186655 (mean inhibition 94 and 42%, respectively). On lung fragments, theophylline and LY 186655 (3 x 10(-5)-3 x 10(-3) M) caused strong and comparable inhibitory effects on anti-IgE (1/500)-induced histamine release with a mean inhibition reaching maximally 65%. Histamine release induced by compound 48/80 (1 mg/ml) on sliced human foreskin was reduced with both drugs (3 x 10(-3) M) by about 37%. We conclude that LY 186655 inhibits in vitro immunological histamine release from human lung and cutaneous mast cells as well as basophils with a similar pattern of activity to theophylline. [less ▲]

Médicaments anti-asthmatiques. De la pharmacologie à la clinique

in Revue Médicale de Liège (1991), 46(2), 58-81

Cutaneous and basophilic sensitivity to substance P and gastrin in non-atopic versus atopic subjects.

in Allergy (1991), 46(1), 30-4

We compared the cutaneous reaction to intradermal injection of substance P, gastrin and histamine in asymptomatic atopic subjects with a history of hay fever and/or asthma versus non-atopic healthy ... [more ▼]

We compared the cutaneous reaction to intradermal injection of substance P, gastrin and histamine in asymptomatic atopic subjects with a history of hay fever and/or asthma versus non-atopic healthy volunteers. We also studied in these two groups the basophilic histamine release induced by substance P and gastrin with that obtained with anti-human IgE and Con A. Intradermal injection of substance P (3-300 pM) and gastrin (3-30 pM) caused a wheal and flare reaction which was comparable in both groups of subjects. Substance P 10(-4)M caused a mean basophilic histamine release of about 15% in atopic and non-atopic subjects. Gastrin was not effective in this model. Anti-IgE and Con A-induced histamine release was significantly higher in atopic than in non-atopic volunteers. [less ▲]

Neurophysins as markers of ADH and oxytocin release

in Hormone Research (1990), 34