Abstract
Insoluble immune complexes (IIC) stimulate human neutrophils through Fc gamma receptors. Freshly isolated human neutrophils express two FcR subclasses, FcRII and FcRIII. We explored the role of FcRII and FcRIII in this activation process by selectively binding each FcR subclass with the Fab fragments of the respective anti-FcR monoclonal antibodies (MFab) before exposure to IIC. Correlation among liganded FcR subclass, IIC binding, and ensuant IIC stimulation was achieved with multiparameter flow cytometry. We utilized rhodamine-labeled anti-FcRIII and fluorescein-labeled IIC to study binding and observed the change in [Ca2+]i in the same cell with a Ca2+ indicator, Indo-1. Treatment with either anti-FcRII (IV.3) or anti-FcRIII (3G8) MFab decreased both the fraction of cells exhibiting a Ca2+ transient and the magnitude of that transient, although only anti-FcRIII but not anti-FcRII significantly inhibited the subsequent IIC binding. In addition, cells treated with anti-FcRII and then stimulated with IIC exhibited a decrease in both the intracellular Ca2+ transient and the later Ca2+ influx, whereas anti-FcRIII totally abolished the mobilization of intracellular Ca2+ without affecting the Ca2+ influx. Treatment with either anti-FcR MFab decreased the IIC-stimulated transmembrane potential change, oxidative burst, and elastase release. These studies indicate that freshly isolated neutrophils' Fc receptor subclasses have unique roles in the IIC-initiated stimulation and that full activation can only be achieved when both FcR subclasses are available.
Highlights
Insoluble immune complexes (IIC) stimulate human elicit PMN responses via Fc receptor-mediated transduction neutrophils through Fcr receptors
Addition, cells treated with anti-FcRII and thenstim- All three Fc receptor subclasses differ in molecular weight, ulated with IIC exhibited a decrease in both the intra- affinity for subclasses of humanand mouse IgG, trypsin cellular Ca2+ transientandthelater
We found that both FcRII and FcRIII are involved in the IIC-induced increase in [Ca2+Ii,change in membrane potential, oxidative burst and release of elastase, but to different extents
Summary
The present studiesassess the functional role of each FcR subclass by 1)correlating each cell's receptor occupancy and stimulus binding with its own transmembrane signals (e.g. changes in [CaZ+loi r membrane potential) and 2) deducing which FcR subclass initiates which cellular responses to IIC (e.g. superoxide and peroxide generation as well as degranulation such as elastase release). We found that both FcRII and FcRIII are involved in the IIC-induced increase in [Ca2+Ii,change in membrane potential, oxidative burst and release of elastase, but to different extents. IIC access to both FcR subclasses is important for the IIC-induced elastase release
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