Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta

Atherosclerosis. 2001 Jun;156(2):267-75. doi: 10.1016/s0021-9150(00)00644-4.


In the early atherosclerotic lesion, monocytes accumulate at sites of inflammation and endothelial injury. Platelet-derived growth factor (PDGF), produced for example by macrophages, is a chemoattractant for smooth muscle cells and possibly also for macrophages. During early differentiation into macrophages, human monocytes (early hMDM) showed lower expression of PDGF alpha-receptor (PDGF-Ralpha) than beta-receptor (PDGF-Rbeta) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BB(L)) but not short (BB(S)) B-chain homodimer. Neither PDGF-AA(S) nor PDGF-AA(L) affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) on PDGF-R expression and migratory response were studied. Only PDGF-Ralpha mRNA was highly upregulated by IFN-gamma. TGF-beta only had minor effects on receptor mRNAs. Upregulation of PDGF-Ralpha levels by IFN-gamma was accompanied by significantly increased migration (chemotaxis) towards PDGF-AA(L) only. Consequently, IFN-gamma modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA(L) on IFN-gamma-stimulated early hMDM. This suggests that PDGF-AA(L) may be involved in attracting activated monocytes to sites of inflammation and injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Electrophoresis, Agar Gel
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma / metabolism*
  • Interferon-gamma / pharmacology
  • Interferons / analysis*
  • Macrophages / physiology
  • Molecular Sequence Data
  • Monocytes / physiology*
  • Probability
  • RNA, Messenger / analysis*
  • Receptors, Platelet-Derived Growth Factor / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology


  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Interferons
  • Receptors, Platelet-Derived Growth Factor