Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages: Influence of IFN-γ and TGF-β

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 α-receptor (PDGF-Rα) than β-receptor (PDGF-Rβ) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BBL) but not short (BBS) B-chain homodimer. Neither PDGF-AAS nor PDGF-AAL affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) on PDGF-R expression and migratory response were studied. Only PDGF-Rα mRNA was highly upregulated by IFN-γ. TGF-β only had minor effects on receptor mRNAs. Upregulation of PDGF-Rα levels by IFN-γ was accompanied by significantly increased migration (chemotaxis) towards PDGF-AAL only. Consequently, IFN-γ modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AAL on IFN-γ-stimulated early hMDM. This suggests that PDGF-AAL may be involved in attracting activated monocytes to sites of inflammation and injury.