Evidence for neuronal expression of functional Fc (epsilon and gamma) receptors - PubMed (original) (raw)

Evidence for neuronal expression of functional Fc (epsilon and gamma) receptors

Hanneke van der Kleij et al. J Allergy Clin Immunol. 2010 Mar.

Abstract

We report that neurons express functional Fc receptors (including FcεR1), that can be activated by antigen, transmit signals along nerve fibers in vitro and in vivo. These results open new avenues of investigation in neurogenic inflammation and allergic diseases.

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Figures

Figure 1

Figure 1

mRNA expression of the subunits of FcεRI, FcγRI-IV, and CD23 in SCG neurons. mRNA was collected from three (1–3) SCG neuronal cultures and expression of the indicated mRNA was measured by RT-PCR. (a) Expression of the α subunit of the low affinity receptors for IgG (FcγRI-IV) and for IgE (CD23). (b, c) Expression of the subunits of FcεRI and of mMCP-1 (C) in SCG neurons derived from Balb/c (a–c) or C57BL/6 (c) mice. Spleen cDNA and mRNA from bone marrow derived mouse mast cells or from B cells were used as positive controls. The mRNA of the mouse IMCD-3 kidney epithelial cell line from the inner medulla collective duct, was a negative control for FcεRI, mMCP-1 and FcγRI, III, and IV expression. A control for PCR contamination was performed using H2O.

Figure 2

Figure 2

Neurons were sensitized with IgE and incubated overnight with antibody against IgE (a, left panel) or with an antibody of unknown specificity (a, right panel). Staining with the neuron specific marker PGP9.5 (b–c, left panel in red) and FcεRIα (b), β (c) or γ-chain (d) (middle panel in green) is shown. Confocal images were overlayed (b–d, right panel); yellow represents merging of red and green colours.

Figure 3

Figure 3

(a) Kinetics of [Ca2+]i increase upon stimulation with scorpion venom (SV, Control) or with anti-DNP IgEa,/b sensitized neurons following Ag stimulation (10 ng/ml). The arrows indicate the time of addition of the stimulus. (b) Confocal image of calcium responses of IgE-sensitized neurons prior to and after Ag addition. (c) Kinetics of [Ca2+]i increase in anti-DNP IgG 1 sensitized neurons after Ag stimulation. (d) Dose response of IgE and IgG-mediated neuron activation.

Figure 4

Figure 4

Activation of interconnected neurites by FcεRI stimulation of a single neuronal cell body. (a) Bright field image of neuron network showing relation of Ag-containing spritzer to neuronal cell body sensitized with IgE anti-DNP. (b) At time zero, beginning of 500ms spritz with Ag (DNP-HSA). (c) 0.5s and (d) 1.8s after onset of spritz.

Figure 5

Figure 5

(A–I) Myenteric ganglion calcium imaging. Spritzer (internal bore, 40 μm) is indicated by dotted lines and myenteric plexus by solid lines. (a–c) Anti-DNP IgE sensitized myenteric neurons were imaged in mast cell-deficient W/Wv mice.a, Resting condition.b, Fluorescent image captured 0.16s after 20ms spritz.c, 4s after spritz. (d–f) No increase in calcium fluorescence was observed in non-haptenated HSA spritz. (g–i) Positive calcium increases in WBB6F1 control littermates. Time sequence same as previous.

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