Aggregation of low affinity IgG receptors induces mast cell adherence to fibronectin: requirement for the common FcR gamma-chain.
Mast cells have been reported to increase at sites of immune complex-induced inflammation where these cells appear to potentiate the inflammatory response. The mechanism by which mast cells accumulate at these sites is unknown. One possibility is that aggregation of low affinity IgG receptors could signal mast cells to adhere to components of the connective tissue matrix. To test this hypothesis, we first added aggregated IgG to a mast cell adhesion assay employing fibronectin as a matrix component and observed an increase in cell adhesion. Even a small amount of aggregated IgG (< 60 ng/ml) demonstrated by fast protein liquid chromatography in untreated IgG preparations was sufficient to increase mast cell adhesion by 100%. We next explored the Fc gamma receptors involved. Fc gammaRII/III, which are receptors for oligomeric IgG and were first verified as present on these mast cells by FACS analysis and immunoprecipitation, signaled mast cells to rapidly adhere to fibronectin when aggregated with the anti-receptor Ab2.4G2. The adhesion process mediated by Fc gammaRII/III was not associated with beta-hexosaminidase release. Bone marrow-cultured mast cells from common gamma-chain deficient mice, unlike mast cells cultured from +/+ mice, did not respond to Fc gammaRII/III aggregation. This demonstrated requirement for a gamma-chain implicates oligomeric Fc gammaRIII in the adhesion process. Thus, aggregation of Fc gammaRIII on mast cells leads to mast cell adhesion, demonstrating a previously unknown biological function for this receptor on mast cells and providing a mechanism for mast cell accumulation in immune complex-dependent inflammation.
Dastych
J
J
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Hardison
M C
MC
Metcalfe
D D
DD
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D017452:Receptors, IgG