Functional expression of IgG-Fc receptors in human airway smooth muscle cells

IgE-Fc receptors and IgG-Fc receptors are expressed on hematopoietic cells, but some evidence suggests that these receptors are also found on non-hematopoietic cells including human airway smooth muscle (hASM) cells. Our study characterized the expression of IgE-Fc receptors (Fc{epsilon}RI/CD23) and IgG-Fc receptors (Fc{gamma}RI, Fc{gamma}RII and Fc{gamma}RIII) in cultured hASM cells by flow cytometry and Western blotting, and the functional activity of receptors was determined through quantification of cell proliferation and released cytokines. Expression of Fc receptor-linked intracellular signaling proteins and phosphorylation of the mitogen-activated protein kinases (MAPK) ERK 1/2 and p38MAPK in hASM cells was examined by Western blotting. Expression of Fc{epsilon}RI and CD23 was not detectable in hASM cells. However, Fc{gamma}RI and Fc{gamma}RII were shown to be expressed on these cells. Specific antibodies, validated using transfected cell lines, revealed that the inhibitory IgG receptor Fc{gamma}RIIb was the most abundant Fc receptor subtype expressed. Whilst cross-linking Fc{gamma}R with heat-aggregated gamma globulin (HAGG) did not induce detectable cell stimulation, pre-treating hASM cells with HAGG significantly inhibited IL-1{alpha}-induced increased cytokine levels and bFGF-induced cell proliferation. This inhibitory effect of HAGG was abrogated by pre-incubation of cells with an anti-Fc{gamma}RIIb Fab fragment. Expression of proteins involved in the canonical Fc{gamma}RIIb inhibitory signaling pathway was established in hASM cells. Pre-treatment of hASM cells with HAGG significantly inhibited IL-1{alpha} ï€ and bFGF-induced ERK1/2 and p38MAPK phosphorylation. This study identifies functional expression of Fc{gamma}RIIb in hASM cells with the potential to suppress their remodeling and immunomodulatory roles