Background: We have reported that canine mastocytoma-derived CM-MC cells are activated via canine IgG and express a high-affinity IgG receptor (canine FcγRI). The predicted amino acid sequence of the canine FcγRI α subunit was found to be 72% similar to that of humans. These results suggest that canine FcγRI have binding activity with human IgG and led us to investigate CM-MC activation via canine FcγRI and human IgG. Methods: The binding of human IgG to canine FcγRI was examined by flow cytometry using FITC-conjugated human IgG. [Ca2+]i increase or histamine release via canine FcγRI and the four human IgG subclasses was measured following aggregation of IgG-bound FcγRIs by anti-human IgG. To determine the binding activity of canine FcγRI with human IgG1 or IgG3, the displacement of 125I-labeled canine IgG from canine FcγRI was examined by unlabeled human IgG1 or IgG3. Results: The fluorescence intensity of CM-MC cells was markedly (about 50 times) elevated by incubation with FITC-human IgG compared with the fluorescence of the control cells. A significant (p < 0.01) calcium response and histamine release were observed following aggregation of canine FcγRIs bound with human IgG1 or IgG4. 125I-labeled canine IgG was displaced from canine FcγRI by preincubation with unlabeled total human IgG or human IgG1 dose-dependently, whereas no displacement was detected by preincubation with human IgG3. Conclusions: Canine FcγRI possesses a significant binding activity with human IgG1 or IgG4, while IgG2 or IgG3 did not significantly react with canine FcγRI on CM-MC cells.

Keywords:
Mast cell, Fc receptor, IgG receptor, Degranulation
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2004
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