Function and regulation of FcεRI expression on monocytes from non-atopic donors

Background The high affinity receptor for IgE (FcεRI) has recently been identified on antigen presenting cells, i.e. Langerhans cells and monocytes from atopic donors and it was hypothesized that FcεRI expression levels correlated with allergy. Objective The aims of the study was to investigate the function and expression of FcεRI on monocytes frotn non-atopic donors. Methods Purified monocytes or peripheral blood mononuclear cells were used to study FcεRI expression and signal transduction on CD14 positive cells by flow cytometry and/or confocal laser microscopy. Results Freshly isolated monocytes from healthy individuals (n = 58) were shown to express FcεRI (median 18%, range 2–66%). No IgE was bound to these receptors in vivo, and in vitro no significant binding of complete IgE molecules could be obtained. IgE positive monocytes from atopic donors were also found to have free FcεRI, incapable of binding IgE in vitro. Oti all CD14 positive cells free FcεRI expression was rapidly and completely lost during culture in conventiotial culture media (IMDM. RPMI) but not in phosphate buffered saline (PBS). Moreover, signal transduction through free FcεRI appeared to be inhibited. However, both IgE binding and calcium mobilization were restored by treatment of fresh non-atopic monocytes with neuraminidase. Importantly, culturing these monocytes overnight in conventional medium containing 2μg/mL IgE induced a cycloheximide insensitive accumulation of IgE bound to FcεRI and, in addition, led to cell activation. Conclusion Monocytes from both atopic donors and healthy individuals express FcεRI, but the previously reported different expression levels between the two groups seem to be directly related to the absence or presence of TgE in the serum. This may be due to the fact that FcεRI is subjected to a constant turnover process which is slowed down but not prevented by ligand binding. In addition, free FcεRI on non-atopic monocytes are under control of a neuramindase sensitive structure(s), which influences signal transduction and IgE binding.