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

• Published in: Atherosclerosis 2001-06, Vol.156 (2), p.267-275
• Main Authors: Krettek, Alexandra, Östergren-Lundén, Gunnel, Fager, Gunnar, Rosmond, Carolina, Bondjers, Göran, Lustig, Florentyna
• Format: Article
• Language: English
• Subjects: Atherosclerosis (general aspects, experimental research); Base Sequence; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Cytokines; Electrophoresis, Agar Gel; Enzyme-Linked Immunosorbent Assay; Humans; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Interferons - analysis; Macrophages; Macrophages - physiology; Medical sciences; Medicin; Migration; Molecular Sequence Data; Monocytes - physiology; PDGF; Probability; Receptor; Receptors, Platelet-Derived Growth Factor - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology
• ISSN: 0021-9150; 1879-1484; 1879-1484
• 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 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 (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-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-AA L only. Consequently, IFN-γ modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA L on IFN-γ-stimulated early hMDM. This suggests that PDGF-AA L may be involved in attracting activated monocytes to sites of inflammation and injury.