IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcepsilonRI in human basophils.
Expression of the high-affinity receptor on basophils and mast cells is modulated by immunoglobulin E (IgE) antibody. Recent studies have shown that modulation occurs through interaction of IgE with the receptor itself, but the mechanisms underlying this control are not understood. Taking both a theoretical and experimental approach, we examined several competing models that focus on whether there is IgE-regulated loss, IgE-regulated synthesis, or both regulated loss and synthesis of the Fc receptor for IgE (FcepsilonRI). We report that removing IgE from occupied FcepsilonRI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE-regulated loss of receptors. An examination of synthetic rates of FcepsilonRIalpha using pulse-labeling with (35)S-methionine indicated no difference in synthetic rates in the presence or absence of IgE. Similarly, the presence or absence of IgE had no influence on the levels of mRNA for either alpha, beta, or gamma subunits of FcepsilonRI. Using model simulations, we found that regulated-synthesis models could be distinguished from regulated-loss/constant-synthesis models on the basis of the relationship between starting FcepsilonRI densities and changes in density after culture for 1 week in the absence of IgE. Experimental data from this type of study fit a regulated-loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of FcepsilonRI only by regulating the rate that receptor is lost from the cell surface.
MacGlashan
D
D
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA. dmacglas@jhmi.edu
Xia
H Z
HZ
Schwartz
L B
LB
Gong
J
J
D001491:Basophils / Q000378:metabolism*; D002478:Cells, Cultured; D003198:Computer Simulation; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E