Immunological Release of Histamine and Slow-Reacting Substance of Anaphylaxis From Human Lung

Abstract

The sensitization of human lung with atopic serum is both time and temperature dependent. Highly purified IgE myeloma protein is capable of blocking sensitization of human lung with atopic serum whereas myeloma proteins of the IgG subgroups are inactive. Drugs capable of increasing cellular levels of CAMP such as ß-adrenergic agents and methylxanthines inhibit the antigen-induced release of both histamine and SRS-A from human lung and these agents demonstrate synergism when used together. The ß-adrenergic blocking agent, propranolol, prevents epinephrine-induced inhibition of the immunologic release of the mediators. Diethylcarbamazine also inhibits the antigen-induced release of histamine and SRS-A from human lung and a synergism between this drug and epinephrine is observed. Predominantly α-adrenergic stimulation achieved by combining propranolol with epinephrine or norepinephrine not only prevented the inhibitory activity of the sympathomimetic amines but also resulted in an enhanced release of histamine and SRS-A. These observations suggest that whereas increases in cellular levels of CAMP are inhibitory, decreases in cellular levels of CAMP enhance the antigen-induced release of the mediators.

Characterization of the adenosine receptor responsible for the inhibition of histamine and SRS‐A release from human lung fragments

“…Although the rank order of potency of adenosine analogues was almost identical for inhibition of the release of both histamine and SRS-A, it appeared that NECA and NCPCA were relatively more effective against the release of SRS-A. A similar observation has been made with both isoprenaline (Orange et al, 1971) and with salbutamol (Butchers et al, 1979). Although having a common trigger in the cross-linking of IgE receptors and occurring in tandem in challenged cells the processes of SRS-A generation and the release of histamine are very different, particularly as only the latter involves the intracellular structural changes of exocytosis.…”

Oral aspirin challenges in asthmatic patients: a study of plasma histamine

“…Histamine has been studied extensively and its role in producing vasodilation {fiushing. peripheral vascular collapse) (Schild, 1956), direct bronchial smooth muscle constriction (Austen, 1971), or activation of bronchial mucosal afferent receptors with reflex cholinergic discharge (Gold, Kessler & Yu, 1972) has been established. Inhalation of histamine in very low concentrations, in the order of 0-03-10 mg/ml of histamine base produces bronchoconstriction in most asthmatic individuals regardless of their clinical asthmatic mechanisms (Spector & Farr, 1975).…”

Effects of theophylline and rolipram on leukotriene C4 (LTC4) synthesis and chemotaxis of human eosinophils from normal and atopic subjects

“…Anti-inflammatory actions of theophylline are reflected by its effects on isolated cell function, in animal experiments and under clinical conditions. With respect to isolated cell functions theophylline has been demonstrated to suppress the generation of reactive oxygen radicals (02) from alveolar macrophages (Dent et al, 1994b), eosinophils and neutrophils (Nielson et al, 1990), eosinophil degranulation and the release of granulocyte-macrophage-colony-stimulating-factor (CM-CSF) from eosinophils (Shute et al, 1995a), monocyte and alveolar macrophage tumour necrosis factor a (TNFa) production (Spatafora et al, 1994), T-lymphocyte chemotaxis (Hidi-Ng et al, 1995) and histamine release from mast cells (Orange et al, 1971;Louis et al, 1992). These anti-in-flammatory effects of theophylline in vitro are translated clinically to a theophylline-induced improvement of airway inflammation in asthmatics.…”