Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1.
The chemotactic factors responsible for complement-independent macrophage accumulation in immune-complex diseases such as glomerulonephritis remain unknown. Fc receptors for IgG complexes are found on mesangial cells of the kidney, which produce the macrophage growth factor colony-stimulating factor 1 (CSF-1). We therefore investigated the possible stimulation of mesangial-cell expression of CSF-1 and the recently identified monocyte-specific chemoattractant protein 1 (MCP-1) by IgG complexes. IgG complexes, but not monomeric IgG or F(ab')2 fragments of IgG, rapidly (2-8 h) increased mRNA for both CSF-1 (10-fold) and MCP-1 (20-fold) in cultured mouse mesangial cells. The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response. IgG complexes also caused a 10-fold increase in the secretion of CSF-1 and a 3- to 5-fold increase in secretion of MCP-1 into the cell culture medium. The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition.
Hora
K
K
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Satriano
J A
JA
Santiago
A
A
Mori
T
T
Stanley
E R
ER
Shan
Z
Z
Schlondorff
D
D
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics*; D004705:Endocytosis; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology*; D005921:Glomerulonephritis / Q000503:physiopathology; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000502:physiology*; D015398:Signal Transduction
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011961:Receptors, Fc; D016173:Macrophage Colony-Stimulating Factor