Nasal challenge with the relevant antigen can induce a late response characterized by local accumulation of eosinophils, neutrophils and mononuclear cells persisting for 48 h and accompanied by release of ECP, MPO, LTB4 and histamine. These results indicate that a single antigen challenge in patients with allergic rhinitis causes prolonged inflammatory alterations which may contribute to the development of airway hyperreactivity.

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Loratadine is a powerful H₁ antagonist commonly employed in the treatment of allergic disorders. The present study was performed to investigate whether loratadine, in addition to anti-H₁ activity, is able to modulate histamine release from human basophils. Leukocyte suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from 10 normal subjects. Leukocytes were stimulated with anti-IgE (1/5,000), N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 μM) and the Ca²⁺ ionophore A23187 (1 μM), and histamine release in the cell supernatants was measured by an automated fluorometric method. Loratadine, at concentrations ranging from 1 to 50 μM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine release. The concentrations inhibiting 50% of histamine release were 30 μM (anti-IgE), 29 μM (FMLP) and 24 μM (Ca²⁺ ionophore A23187). The inhibitory activity of loratadine was optimal after incubation for 2 h at 37°C and the effect of the drug was no longer evident when leukocytes were stimulated 2 h after cell washing. Increased extracellular Ca²⁺ concentrations reduced the inhibitory activity of loratadine, indicating that external Ca²⁺ and loratadine have antagonistic effects on basophil histamine release. These results indicate that loratadine, in addition to H₁ receptor blocking activity, has the capacity to inhibit histamine release from human basophils.

N Na as sa al l e eo os si in no op ph hi il li ia a i in nd du uc ce ed d b by y P PA AF F--a ac ce et th he er r i is s a ac cc co om mp pa an ni ie ed d b by y t th he e r re el le ea as se e o of f e eo os si in no op ph hi il l c ca at ti io on ni ic c p pr ro ot te ei in n A. Tedeschi, N. Milazzo, A. Miadonna Nasal eosinophilia induced by PAF-acether is accompanied by the release of eosinophil cationic protein. A. Tedeschi, N. Milazzo, A. Miadonna. ERS Journals Ltd 1994. ABSTRACT: It has been demonstrated that platelet-activating factor (PAF)-acether can induce nasal neutrophilia and eosinophilia, with a different degree of responsiveness in atopic and in nonatopic subjects. The aim of this study was to evaluate whether PAF can also induce the release of secondary mediators in the human nose. Ten patients with allergic rhinitis and 10 normal subjects underwent nasal challenge with PAF (500 nmol), lyso-PAF (500 nmol) and saline solution. Nasal lavages were performed before and after challenge to evaluate changes in nasal cytology and release of histamine, immunoreactive leukotriene (iLT) C 4 and eosinophil cationic protein (ECP).PAF caused neutrophilia and eosinophilia, which appeared earlier in atopic than in nonatopic subjects (30 min vs 1 h), and peaked 3 h after challenge in both groups. Lyso-PAF caused mild neutrophilia, which appeared 3 h after challenge in both groups; an increase in eosinophil counts was observed 3 h after challenge in atopic subjects, but not in nonatopic subjects. PAF insufflation caused a significant release of ECP in nasal lavage fluids 30 min and 3h after challenge in atopic subjects, and 3 h after challenge in nonatopic subjects. ECP levels in the nasal lavages collected 30 min and 3 h after challenge with PAF were higher in atopic than in nonatopic subjects. Eosinophil counts correlated with ECP levels in the nasal lavages collected 30 min after PAF challenge in atopic subjects. Nasal challenge with lyso-PAF did not provoke any release of ECP. No significant increase of histamine and iLTC 4 levels in nasal lavages was found after challenge with either PAF or lyso-PAF.These results indicate that PAF-induced nasal eosinophilia is accompanied by ECP release, which appears earlier and is more marked in atopic than in nonatopic subjects.

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The effects of copper (CuSO4 and CuCl2) on in vitro histamine release from human basophils stimulated by anti-IgE and Ca2+ ionophore A23187 were evaluated. Both CuSO4 and CuCl2 caused a dose-related inhibition of histamine release, which was more pronounced on anti-IgE- than on Ca2+ ionophore-induced histamine release. The concentration which produced 50% inhibition of anti-IgE-induced histamine release was 1.3 microM for CuSO4 and 1.5 microM for CuCl2; the maximal inhibition of Ca2+ ionophore-induced histamine release was 33% for CuCl2 (4 microM) and 51% for CuSO4 (16 microM). The inhibitory effect on anti-IgE-induced histamine release persisted also when extracellular Cu2+ was removed by cell washing before stimulation, whereas no inhibition of Ca2+ ionophore-induced histamine release was found when extracellular Cu2+ was removed. The activity of Cu2+ was independent of any effects of deuterium oxide and colchicine, two agents known to interact with microtubules. Increased extracellular Ca2+ concentrations reduced the inhibitory effect of CuCl2 on Ca2+ ionophore-induced histamine release, and Schild plot analysis demonstrated that Cu2+ ions are competitive antagonists of Ca2+ ions. These results indicate that Cu2+ ions in the micromolar range down-regulate anti-IgE- and Ca2+ ionophore-induced histamine release. Since Cu2+ concentration in human plasma is in the micromolar range (30 microM with 10-30% of free Cu2+), it is conceivable that Cu2+ ions contribute to the in vivo regulation of histamine release from human basophils.

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