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IgE-Fc receptors and IgG-Fc receptors are expressed on hematopoietic cells, but some evidence suggests that these receptors are also found on nonhematopoietic cells, including human airway smooth muscle (hASM) cells. Our study characterizes the expression of IgE-Fc receptors (FcepsilonRI/CD23) and IgG-Fc receptors (FcgammaRs-I, -II, and -III) 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 (MAPKs) extracellular signal-regulated kinase ½ and p38(MAPK) in hASM cells was examined by Western blotting. Expression of FcepsilonRI and CD23 was not detectable in hASM cells. However, FcgammaRI and FcgammaRII were shown to be expressed on these cells. Specific antibodies, validated using transfected cell lines, revealed that the inhibitory IgG receptor, FcgammaRIIb, was the most abundant Fc receptor subtype expressed. Although cross-linking FcgammaR with heat-aggregated gamma globulin (HAGG) did not induce detectable cell stimulation, pretreating hASM cells with HAGG significantly inhibited IL-1alpha-induced increases in cytokine levels and basic fibroblast growth factor-induced cell proliferation. This inhibitory effect of HAGG was abrogated by preincubation of cells with an anti-FcgammaRIIb antigen-binding fragment (Fab). Expression of proteins involved in the canonical FcgammaRIIb inhibitory signaling pathway was established in hASM cells. Pretreatment of hASM cells with HAGG significantly inhibited IL-1alpha- and basic fibroblast growth factor-induced extracellular signal-regulated kinase ½ and p38(MAPK) phosphorylation. This study identifies functional expression of FcgammaRIIb in hASM cells, with the potential to suppress their remodeling and immunomodulatory roles.