Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta.
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.
Krettek
A
A
Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, 413 45, Göteborg, Sweden.
Ostergren-Lundén
G
G
Fager
G
G
Rosmond
C
C
Bondjers
G
G
Lustig
F
F
D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D007372:Interferons / Q000032:analysis*; D008264:Macrophages / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D007372:Interferons; D017479:Receptors, Platelet-Derived Growth Factor