Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta
2001 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 156, no 2, 267-275 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier, 2001. Vol. 156, no 2, 267-275 p.
Cytokines, Macrophages, Migration, PDGF, Receptor
Other Basic Medicine
Research subject Medical sciences
IdentifiersURN: urn:nbn:se:his:diva-11409DOI: 10.1016/S0021-9150(00)00644-4ISI: 000169476700003PubMedID: 11395022ScopusID: 2-s2.0-0034995007OAI: oai:DiVA.org:his-11409DiVA: diva2:848235