Analysis of Fc(epsilon)RI-mediated mast cell stimulation by surface-carried antigens.
Clustering of the type I receptor for IgE (Fc[epsilon]RI) on mast cells initiates a cascade of biochemical processes that result in secretion of inflammatory mediators. To determine the Fc(epsilon)RI proximity, cluster size, and mobility requirements for initiating the Fc(epsilon)RI cascade, a novel experimental protocol has been developed in which mast cells are reacted with glass surfaces carrying different densities of both antigen and bound IgE, and the cell's secretory response to these stimuli is measured. The results have been analyzed in terms of a model based on the following assumptions: 1) the glass surface antigen distribution and consequently that of the bound IgE are random; 2) Fc(epsilon)RI binding to these surface-bound IgEs immobilizes the former and saturates the latter; 3) the cell surface is formally divided into small elements, which function as a secretory stimulus unit when occupied by two or more immobilized IgE-Fc(epsilon)RI complexes; 4) alternatively, similar stimulatory units can be formed by binding of surface-carried IgE dimers to two Fc(epsilon)RI. This model yielded a satisfactory and self-consistent fitting of all of the different experimental data sets. Hence the present results establish the essential role of Fc(epsilon)RI immobilization for initiating its signaling cascade. Moreover, it provides independent support for the notion that as few as two Fc(epsilon)RIs immobilized at van der Waals contact constitute an "elementary stimulatory unit" leading to mast cell (RBL-2H3 line) secretory response.
Schweitzer-Stenner
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R
Institut für Experimentelle Physik, Universität Bremen, Germany.
Tamir
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Pecht
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D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000378:metabolism; D055592:Biophysical Phenomena; D001703:Biophysics; D002460:Cell Line; D004140:Dinitrophenols / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D007073:Immunoglobulin E / Q000008:administration & dosage / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D013499:Surface Properties
D000941:Antigens; D004140:Dinitrophenols; D018836:Inflammation Mediators; D017455:Receptors, IgE; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E