Inhibition of IgE‐dependent histamine release from human dispersed lung mast cells by anti‐allergic drugs and salbutamol

Abstract

The ability of the anti‐allergic drugs, sodium cromoglycate (SCG), lodoxamide, traxanox, RU31156 and the β‐adrenoceptor agonist sulbutamol to inhibit IgE‐dependent histamine and prostaglandin D2 (PGD2) release was assessed using human dispersed lung mast cells. The anti‐allergic drugs were weak inhibitors of histamine release, high concentrations (100–1000 μm) producing < 35% inhibition. Salbutamol produced 39% inhibition at 10 μm. The efficacy of both SCG and salbutamol was inversely related to the concentration of anti‐IgE used for challenge and to the degree of histamine release. Rapid tachyphylaxis was observed with all anti‐allergic drugs but not with salbutamol. Cross‐tachyphylaxis was observed between SCG and the other anti‐allergic drugs, suggesting a common mechanism of action. No cross‐tachyphylaxis was observed between SCG and salbutamol. SCG was significantly (P < 0.001) more effective in inhibiting PGD2 than it was histamine release. Preferential inhibition of PGD2 compared with histamine release was less marked (P < 0.05) with salbutamol and not significant with the other anti‐allergic drugs. Mast cells dispersed by enzymatic digestion of human lung released more histamine on immunological challenge than mechanically dispersed cells obtained by fine chopping of tissue. Enzyme treatment of mechanically dispersed cells removed this difference. Enzymatically and mechanically dispersed cells responded similarly to the inhibitory effects of SCG and salbutamol. Our results suggest that salbutamol is a more effective inhibitor of mediator release from human lung mast cells than anti‐allergic drugs. However, with the low levels of mediator release achieved during an allergic reaction in man in vivo, both salbutamol and SCG are likely to be effective inhibitors of both preformed and newly generated mediators.

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation

“…In contrast to the results with PDE inhibitors and beclomethasone, salbutamol was effective in suppressing mast cell-derived histamine release. This is consistent with the findings of both Peters et al (1982) and Church & Hiroi (1987) who demonstrated that02 agonists could inhibit histamine release from human dispersed mast cells, an effect mediated by /2 receptors present on mast cells in human lung (Butchers et al, 1980). …”

Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons

“…In addition, histamine is a transmitter molecule in inflammatory processes and induces burning sensations (63)(64)(65)(66)(67), leading to itching or pain (68,69). Histamine release occurs from vesicles in mast cells or basophils in IgE-mediated allergic reactions (70). This leads to the activation of keratinocytes, which in turn release a transmitter to excite free nerve endings in the epidermis.…”

Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcϵRI

“…[4][5][6][7][8][9] However, it has become clear that rodent MCs are somewhat different from their human counterparts in terms of their sensitivity to some cytokines and drugs and their receptor expression profiles such as for Fc␥R. 3,[10][11][12][13] It is also observed that the level of IgE-dependent TNF-␣ production by human MCs is quite low compared to that by rodent MCs. 3,4,14 Therefore, it is now necessary to determine if human MCs express TLR4.…”