calcimycin and Rhinitis--Allergic--Seasonal

Preliminary studies in hematological patients have indicated that treatment with rhG-CSF reduces basophil releasability ex vivo. We examined this phenomenon further, in allergic patients. Ten patients with grass pollen rhinoconjunctivitis were given rhG-CSF (5 micrograms/kg/day s.c.) for 5 days, and examined before and after treatment. Basophil counts increased from 5 to 19 x 10(9)/l (P < 0.01). Total blood histamine increased from 80 to 160 micrograms/l (P < 0.01), corresponding to a decrease in average basophil histamine content from 1.5 to 0.81 pg/cell (P < 0.01). Isolated mononuclear cells showed a significantly decreased histamine release (HR) when stimulated with A23187 and grass. Whole blood experiments showed a similar decreased HR to grass and anti-IgE (P < 0.01). However, we found an increase in total blood histamine. We conclude that treatment with rhG-CSF (1) increases the number of circulating blood basophils, (2) reduces the average histamine content per basophil, and (3) reduces the basophil releasability. These findings could be due to the mobilization of immature basophils from the bone marrow.

Topics: Adult; Basophils; Calcimycin; Granulocyte Colony-Stimulating Factor; Histamine Release; Humans; Hypersensitivity; In Vitro Techniques; Leukocyte Count; Middle Aged; Pollen; Recombinant Proteins; Rhinitis, Allergic, Seasonal

Loratadine, a new nonsedating histamine H1-antagonist, has been shown to inhibit immunologic release of inflammatory mediators in addition to its H1-receptor blocking properties. After oral administration, the agent is metabolized primarily to desethoxycarbonyl-loratadine (DCL). The basic piperidine, DCL, is readily soluble in water, whereas the nonbasic urethane, loratadine, is insufficiently soluble in water for some in vitro investigations. Therefore we used the metabolite, DCL, to study its influence on in vitro leukocyte histamine release (LHR) in 24 allergic and 22 nonallergic subjects. IgE-mediated and calcium ionophore A23187-induced LHR were inhibited by DCL in a dose-dependent fashion (values of drug concentration to induce 30% inhibition after stimulation with inhalant antigen, anti-IgE, concanavalin A, and calcium ionophore A23187 were 6, 8, 5, and 11 mumol/L, respectively). Higher concentrations of DCL caused mediator release in all subjects (n = 45, 30 mumol/L DC: 11% +/- 2% LHR, 100 mumol/L DCL: 35% +/- 1% LHR), abolishing any inhibitory effect of the drug. Rapid onset of inhibition by 10 mumol/L DCL was found in kinetic studies (n = 10). The inhibition of anti-IgE-induced histamine secretion was synergistically increased by simultaneous preincubation of DCL with the potent histamine H2-agonist, FRA-19. Additional data indicate that the inhibition of LHR by DCL might involve biochemical events that occur after cellular Ca++ influx because LHR induced by N-formyl-methionyl-leucyl-phenylalanine or the phorbol ester, 12-O-tetradecanoyl phorbol-12-acetate, was not significantly affected by DCL.

Topics: Basophils; Calcimycin; Concanavalin A; Histamine H1 Antagonists; Histamine Release; Humans; Immunoglobulin E; In Vitro Techniques; Loratadine; N-Formylmethionine Leucyl-Phenylalanine; Rhinitis, Allergic, Seasonal; Tetradecanoylphorbol Acetate

We evaluated basophil releasability in two groups of allergic patients with positive skin tests to Dermatophagoides pteronyssinus major allergen (Der p l) (29 adults with bronchial asthma and 17 with allergic rhinitis) and in 31 age-matched normal donors. Both basophil reactivity (maximal percent histamine release) and basophil sensitivity (the concentration that causes 50% of maximal percent histamine release: HC50) to Der p l in patients with asthma were similar to those in patients with allergic rhinitis. On the contrary, basophil reactivity to anti-IgE was significantly higher in patients with asthma (58.0 +/- 3.6%) than in patients with allergic rhinitis (46.3 +/- 5.2%; p less than 0.05). Both groups of patients showed an increased releasability compared to control subjects (27.3 +/- 4.6%; p less than 0.001), whereas there were no significant differences in basophil sensitivity to anti-IgE among the three groups of donors. Differences were also found with respect to basophil reactivity and sensitivity to f-met peptide, whereas no differences appeared when basophils from the three groups of donors were challenged with the Ca2+ ionophore A23187. There was a significant correlation between basophil reactivity and sensitivity to Der p l and to anti-IgE in both asthmatic and allergic rhinitis patients. A significant correlation was found between basophil reactivity and sensitivity to anti-IgE and serum IgE level only in patients with bronchial asthma, whereas no correlations were found in patients with allergic rhinitis. There was no correlation between in vivo mast cell releasability and in vitro basophil releasability in response to Der p l in either group of allergic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Animals; Antigens; Asthma; Basophils; Calcimycin; Child; Female; Histamine Release; Humans; Immunoglobulin E; Male; Mites; N-Formylmethionine Leucyl-Phenylalanine; Rhinitis, Allergic, Seasonal; Skin Tests

We determined the relationship of allergic disease to the number and activity of eosinophils and their production of leukotriene B4 and leukotriene C4 (leukotriene D4 equivalents). Granulocytes from allergic rhinitis (AR) subjects and asthmatics release more LTC4 than normals. Furthermore, eosinophils of asthmatics generate more LTC4 than those of AR subjects.

Topics: Adult; Asthma; Calcimycin; Eosinophils; Female; Granulocytes; Humans; Leukocyte Count; Leukotriene B4; Male; Middle Aged; Reference Values; Rhinitis, Allergic, Seasonal; SRS-A; Statistics as Topic

It has been suggested that IgE-dependent basophil histamine release (HR) does not necessarily relate to the amount of cell-bound IgE and, therefore, basophil "releasability" must be considered an important factor in this secretory process. To compare an IgE-dependent basophil HR process in nonatopic subjects and patients with allergic rhinitis, concanavalin A (Con A) was used as a secretagogue to stimulate mediator secretion. In 1.0 mmol/L of calcium-containing buffer, basophil HR to Con A (3.0 mcg/ml) was 50.2 +/- 8.6% in patients with allergic rhinitis and only 10.1 +/- 3.9% in nonatopic subjects. To evaluate whether this enhanced HR might be related to increased membrane influx of calcium, the following strategy was followed. Strontium (3.0 and 10.0 mmol/L) enhances immunologic (IgE) release of basophil histamine. Although the mechanism for strontium enhancement is not established, strontium may pass through the membrane channel more easily than calcium to increase secretion. We reasoned that if the enhanced release of histamine to Con A was related to increased membrane permeability to calcium, stimulation of basophil histamine secretion in the presence of strontium would reduce this difference. In both nonatopic subjects and patients with allergic rhinitis, strontium (3.0 and 10.0 mmol/L) enhanced HR. Enhanced HR with strontium was greater with basophils from normal subjects than from subjects with allergic rhinitis. Whether our observations with strontium indicate that the enhanced histamine releasability to Con A in subjects with allergic rhinitis may, in part, be due to a greater influx of calcium after immunologic stimulation must await characterization of the strontium effect or direct measurements of calcium ion disposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Basophils; Buffers; Calcimycin; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Histamine Release; Humans; Immunoglobulin E; Male; Rhinitis, Allergic, Seasonal; Strontium