Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes.
The chemotactic activities of three different isoforms of platelet-derived growth factor (PDGF) on fibroblasts, monocytes, and granulocytes of human origin were investigated. PDGF-AB and PDGF-BB induced strong, dose-dependent responses in both fibroblasts and monocytes, whereas PDGF-AA did not stimulate chemotaxis of these cell types. Instead, PDGF-AA inhibited the chemotactic activity of PDGF-AB and PDGF-BB on fibroblasts and monocytes. However, PDGF-AA was not able to block monocyte chemotaxis induced by FMLP. In contrast, in granulocytes, dose-dependent chemotactic responses were obtained with all three isoforms of PDGF. All isoforms gave maximal responses at concentrations between 5 and 20 ng/ml. At higher concentrations the migration was reduced. Reduction and alkylation of the PDGF molecule, which leads to loss of the mitogenic activity, also caused a loss of the chemotactic activities for all three cell types. The data suggest that the various isoforms of PDGF stimulate and inhibit chemotaxis in an isoform- and cell type-specific manner.
Siegbahn
A
A
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Hammacher
A
A
Westermark
B
B
Heldin
C H
CH
D000478:Alkylation; D002633:Chemotaxis / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010084:Oxidation-Reduction; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017479:Receptors, Platelet-Derived Growth Factor