Surface FceRI expression

Kalesnikoff J. Rios EJ, Chen CC, Alejandro Barbieri M. Tsai M. Tam SY, Galli SJ Roles of RabGEFl/ Rabex-5 domains in regulating FccRI surface expression and FceRI-dependent responses in mast cells. Blood 2007 109 5308-5317. 

Ra C, Jouvin MH, Kinet JP. Complete structure of the mouse mast cell receptor for IgE (FceRI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem 1989 264 15323-15327. 

It may be important to note that there seems to be a dissociation between the synthesis of FceRI subunits and the cell surface expression of this receptor in human eosinophils. Indeed, Smith et al. (52) confirmed the presence of intracellular FceRla protein, using flow cytometry to analyze permeabilized cells as well as immunohistochemistry to directly visualize cytospin preparations, but negligible FceRla protein was detectable on the cell surface. Furthermore, Semi-... 

Studies in both mice (22) and human (23) mast cells parallel the findings discussed above for human peripheral blood basophils. High-affinity receptors (FceRI) on the surface of mast cells are regulated by ambient concentrations of IgE. IgE is known to modulate the expression of FceRII on B cells, where IgE appears to stabilize the cell-surface expression of FceRII by preventing its proteolytic cleavage (24). 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

The initial event in the activation of mast cells for mediator release is the binding of IgE antibodies to the high-affinity 10 M) FceRI IgE receptor abundantly expressed on the mast cell and basophil surfaces. 

The next four factors partially determine how many molecules of antigen-specific IgE reside on fhe surface of the mast cell or basophil. Eor example, if a mast cell has 100,000 FceRI receptors, the total IgE concentration is 1000 ng/ mL, and the antigen specific IgE titer is 200 ng/mL, then 20,000 receptors will be occupied by the antigen-specific IgE (because the occupancy of the receptor is determined by the very high association constant between this receptor and IgE and when the IgE concentration is this high, it is simpler to state the numbers as if all receptors were occupied—the numbers will be valid within 2-3%). As will be explored in greater detail in the next section, the total IgE concentration also determines the expression of FceRI, so that a ratio of specific to total IgE of 20%, as in the example above, has a far different consequence if the total IgE concentration is 10 ng/mL vs. 1000 ng/mL. Since the IgE concentration determines receptor expression, the ability of IgE antibody to be present outside the vascular compartment also determines the ability of mast cells to respond to antigen. 

Surface FceRI expression on peripheral blood eosinophils has been variably observed in vivo since the first report of the high-affinity receptor on blood eosinophils (90) and remains a topic of controversy (91). The initial description involved blood eosinophils from subjects with hypereosinophilic syndromes (90), but subsequent studies have failed to reproduce these observations (85,92). Blood eosinophils express both mRNA and intracellular protein for the a and y subunits of the FceRI receptor complex but lack the P subunit protein. Eosinophils in culture with IL-5 release the a subunit protein into the culture supernatant, but the addition of IgE failed to induce expression of the receptor on the cell surface... 

Finally, the expression levels of FceRI vary not only according to the pathology, but also probably according to the maturation stage and or tissue localization of eosinophils, as suggested by the fact that peritoneal or splenic eosinophils from IL-5 X hFceRIa Tg mice expressed more receptors at their surface than bone marrow or blood eosinophils (D. Dombrowicz et al., unpublished). 

Smith SJ, Ying S, Meng Q, Sullivan MHF, Barkans J, Kon OM, Sihra B, Larche M, Levi-Shaffer F, Kay AB. Blood eosinophils from atopic donors express messenger RNA for the a, P, and y subunits of the high-affinity IgE receptor (FceRI) and intracellular, but not cell surface, a subunit protein. J Allergy CUn Immunol 2000 105 309-317. 

It now seems that many of the uptake mechanisms used by macrophages have also been adopted by DCs. Thus, most of the work to date on DC receptor-mediated endocytosis of soluble antigen has centered around the mannose receptor (44,45), although DCs also express surface DEC 205 (46), FceRI (47), and FcyR (45). Recently, several studies have highlighted the importance of the mannose receptor in DC-mediated endocytosis (48,49). We (McWilliam and Gehr) have preliminary evidence suggesting that monocyte-derived DCs have surface receptors specific for surfactant proteins A and D. This observation also suggests another mechanism by which particulate material, such as bacteria and viruses, can be taken up by DCs and allows an element of opsonization to be included. 

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