Basophil human studies

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

Regarding human tissues, the few data available are contradictory, since according to some authors (Tedeschi et al., 1991) histamine release from basophils is not modified by H3 receptor ligands. In other studies (Bent et al., 1991), it was found that thioperamide could increase histamine release from adenoidal mast cells, but apparently (R)a-methylhistamine was totally inactive. In any case the concentrations of thioperamide are much higher than those necessary to block H3 receptors, thus suggesting that other mechanisms might be involved. Raible et al., (1994) hypothesized by the use of thioperamide, the presence of H3 receptors on human eosinophils which mediate histamine-induced increase in cytosolic calcium mobilization. However, the low efficacy of the known H3 receptor agonists, -as stimuli for eosinophils... 

The studies of mast cell cytokine production described above have shown that maximal induction of cytokine synthesis and release usually occurs in response to IgE-dependent activation. In common with many cell types, there is evidence that FccRI on mast cells is coupled to the phospholipase C effector system that controls two distinct signal transduction pathways, one regulated by Ca " ions and the other by protein kinase C (PKC). Exocytotic degranulation is associated with an increased cytoplasmic level of Ca ions, and activation of mast cells can be therefore achieved by the use of calcium iono-phores which raise intracellular calcium concentrations through a receptor-independent mechanism. Alternative mast cell stimuli include phorbol-12-myristate-13-acetate (PMA) which activates PKC and induces mediator secretion from basophils and rodent mast cells but not from human mast cells, and concanavalin A (Con A), a lectin which can stimulate mast cells by cross-linking of cell-bound IgE and/or cell surface glycoproteins. 

A recent study by Brunner a al. (1993) has confirmed that mature human basophUs synthesize and release IL-4. For optimal secretion, priming with IL-3 for 18-48 h before activation with anti-IgE was required, although low amounts of IL-4 were occasionally detected following incubation with either IL-3 or anti-IgE alone. No spontaneous IL-4 production was detected, and other cytokines known to enhance basophil mediator release, namely IL-5, GM-CSF and nerve growth factor (NGF),... 

Hastie, R, Heroy, J.H. and Levy, D.A. (1979). Basophil leukocytes and mast cells in human nasal secretions and scrapings studied by light microscopy. Lab. Invest. 40, 554-561. 

Topical tacrolimus suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during the initial skin immune response [97]. The inhibitojy effect of tacrolimus on the production of cytokines in T cells has been demonstrated in both Thl and Th2 cells [98]. This is coincident with reports that the transcription factor NEAT, a target for the calcium-regulated phosphatase calcineurin, mediates transcription of both Thl- and Th2-derived cytokines [99]. The effects of tacrolimus on other inflammatory cells such as skin mast cells, basophils, eosinophils, and Langerhans cells have also been studied extensively. Tacrolimus has been shown to inhibit histamine release and cytokine production from human skin, lung, and cord blood-derived cultured mast cells [100-102]. Tacrolimus has also been reported to have a direct inhibitory activity on eosinophil activation [103,104]. 

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