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 nonhematopoietic cells, including human airway smooth muscle (hASM) cells. Our study characterizes the expression of IgE-Fc receptors (FcεRI/CD23) and IgG-Fc receptors (FcγRs-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 1/2 and p38(MAPK) in hASM cells was examined by Western blotting. Expression of FcεRI and CD23 was not detectable in hASM cells. However, FcγRI and FcγRII were shown to be expressed on these cells. Specific antibodies, validated using transfected cell lines, revealed that the inhibitory IgG receptor, FcγRIIb, was the most abundant Fc receptor subtype expressed. Although cross-linking FcγR with heat-aggregated γ globulin (HAGG) did not induce detectable cell stimulation, pretreating hASM cells with HAGG significantly inhibited IL-1α-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-FcγRIIb antigen-binding fragment (Fab). Expression of proteins involved in the canonical FcγRIIb inhibitory signaling pathway was established in hASM cells. Pretreatment of hASM cells with HAGG significantly inhibited IL-1α- and basic fibroblast growth factor-induced extracellular signal-regulated kinase 1/2 and p38(MAPK) phosphorylation. This study identifies functional expression of FcγRIIb in hASM cells, with the potential to suppress their remodeling and immunomodulatory roles.
Xia
YuXiu C
YC
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Schuliga
Michael
M
Shepherd
Malcolm
M
Powell
Maree
M
Harris
Trudi
T
Langenbach
Shenna Y
SY
Tan
Peck Szee
PS
Gerthoffer
William T
WT
Hogarth
P Mark
PM
Stewart
Alastair G
AG
Mackay
Graham A
GA
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007107:Immune System; D007074:Immunoglobulin G / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D009130:Muscle, Smooth / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011961:Receptors, Fc / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007074:Immunoglobulin G; D011961:Receptors, Fc; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases