Dissociation of the chemotactic and mitogenic activities of platelet-derived growth factor by human neutrophil elastase.
Because platelet-derived growth factor (PDGF) may be released at sites where neutrophil proteinases may also be released, we examined the effects of neutrophil elastase and cathepsin G upon the chemotactic and mitogenic activities of PDGF. Elastase abolished the chemotactic activity of PDGF for fibroblasts but had no effect on its chemotactic activity for monocytes, or on its mitogenic activity for 3T3 cells or its capacity to bind to 3T3 cells. Cathepsin G had no effect upon the chemotactic or mitogenic activities of PDGF. In contrast, trypsin eliminated the chemotactic activity of PDGF for monocytes and fibroblasts and the mitogenic activity of PDGF. After reduction and alkylation, PDGF retained full chemotactic activity for fibroblasts and monocytes but exhibited no mitogenic activity and only limited binding to 3T3 cells. These results indicate separate domains on PDGF for fibroblast chemotactic and mitogenic activity and for monocyte and fibroblast chemotactic activity and raise the possibility that the biological activities of PDGF may be modified selectively in vivo. The findings further suggest that the majority of PDGF receptors on fibroblasts mediate mitogenic activity and that only a minority of the PDGF receptors on fibroblasts are responsible for chemotactic activity.
Senior
R M
RM
Huang
J S
JS
Griffin
G L
GL
Deuel
T F
TF
D000478:Alkylation; D002634:Chemotaxis, Leukocyte; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008934:Mitogens; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase; D010446:Peptide Fragments / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013329:Structure-Activity Relationship
D008934:Mitogens; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor; D010196:Pancreatic Elastase