IFN-gamma induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells.
The deposition of immune complexes, followed by activation of complement and/or Fc receptors and generation of chemoattractants, is the most common feature of human glomerulonephritis. Recently we have shown that primary cultured human glomerular mesangial cells (HMC), which are normally negative for IgG Fc receptors, can be stimulated to express the low-affinity FcgammaRIII-A receptor isoform. In this study we further demonstrate that activation of HMC through IFN-gamma resulted in the functional expression of the high-affinity Fc receptor for IgG (FcgammaRI, CD64). IFN-gamma-dependent induction of classical FcgammaRIa1 mRNA as well as a2, b2 splice variants were evident after 24 h in proliferating HMC and after 48 h in resting HMC. Transcription of FcgammaRI mRNA was also induced by IL-10 in proliferating HMC, whereas other cytokines such as IL-3, transforming growth factor-beta1 and granulocyte-macrophage colony-stimulating factor were not effective. Cell surface expression of FcgammaRI could be detected by flow cytometric analysis after IFN-gamma stimulation and was accompanied by the augmentation of MHC class II and the up-regulation of intercellular adhesion molecule-1 expression. Triggering of HMC by cross-linking FcgammaRI with F(ab')2 fragments of the anti-CD64 monoclonal antibody 22 led to enhanced synthesis of mRNA for the chemokines IL-8 and monocyte chemoattractant protein-1, indicating that the FcgammaRI of HMC is functionally active. These in vitro data suggest that engagement of both FcgammaRI and FcgammaRIII-A on activated HMC through IgG immune complexes may result in an increased chemoattraction of leukocytes into the glomerulus, contributing to the development of glomerulonephritis.
Uciechowski
P
P
Institute of Clinical Molecular Pharmacology, Medical School, Hannover, Germany.
Schwarz
M
M
Gessner
J E
JE
Schmidt
R E
RE
Resch
K
K
Radeke
H H
HH
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017452:Receptors, IgG / Q000819:agonists* / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma