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Inducing an Anergic State in Human Mast Cells (MC) and Basophils (HB) without Secretion
Author(s) -
MacGlashan Donald W,
Undem Bradley J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1075.5
Subject(s) - syk , secretion , histamine , antigen , chemistry , stimulation , immunology , microbiology and biotechnology , receptor , biology , pharmacology , endocrinology , biochemistry , tyrosine kinase
IgE‐mediated secretion from MC or HB depends on the activity of both syk and PI3K but several specific down‐regulatory pathways (e.g., loss of syk expression) do not. We tested whether stimulation with antigen, in the presence of a syk inhibitor (SI = NVP‐QAB205) would ablate secretion while simultaneously allowing anergy. The anergic state was assessed after a relatively short period of time (45–60 min.) by removing the SI and re‐stimulating the cells. HB, cultured‐derived MC and in situ stimulated airway MC (human bronchi) were examined. Antigen caused 35 ±65% and 62 ±10% histamine release from HB and MC, respectively; and it caused an 87±5% histamine/LTD4‐dependent contraction of bronchi. All of these responses were blocked > 95% by the SI. Re‐challenging the preparations with antigen, after first washing out the SI and antigen, revealed that near complete anergy (92–100%) occurred in each case. In control experiments we demonstrated that the SI was readily reversible and easily washed out of the cells and tissues. Thus, even though the SI nearly abolished the antigen‐induced secretion from MC and HB, it had little effect on the pathways involved in anergy. A similar result was found when using a PI3K inhibitor, LY294002. These results suggest that syk and PI3K are not involved in down‐regulation leading to anergy and that it would be possible to induce anergy in vivo without a significant induction of MC/HB secretion.