Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1

Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1745-9. doi: 10.1073/pnas.89.5.1745.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cells, Cultured
  • Chemokine CCL2
  • Chemotactic Factors / genetics*
  • Endocytosis
  • Gene Expression
  • Glomerular Mesangium / cytology*
  • Glomerulonephritis / physiopathology
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism*
  • In Vitro Techniques
  • Macromolecular Substances
  • Macrophage Colony-Stimulating Factor / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • Receptors, Fc / physiology*
  • Signal Transduction

Substances

  • Chemokine CCL2
  • Chemotactic Factors
  • Immunoglobulin G
  • Macromolecular Substances
  • RNA, Messenger
  • Receptors, Fc
  • Macrophage Colony-Stimulating Factor