Human microvascular endothelial cells express receptors for platelet-derived growth factor.
Endothelial cells have been widely thought to be unresponsive to platelet-derived growth factor (PDGF, a major growth factor released from stimulated platelets at the sites of vascular insults) and devoid of PDGF receptors. Nevertheless, in examining the growth-factor responses of microvascular endothelial cells isolated from human omental adipose tissue, we were surprised to detect PDGF-induced tyrosine phosphorylation of a 180-kDa glycoprotein, subsequently identified as the cellular receptor for PDGF by specific immunoprecipitation. Scatchard analysis of 125I-labeled PDGF binding to human microvascular endothelial cells revealed 30,000 PDGF receptors per cell with a Kd of 0.14 nM. PDGF stimulated tyrosine phosphorylation of PDGF receptors and other cellular proteins in a dose- and time-dependent manner, with half-maximal receptor phosphorylation occurring at 0.3 nM recombinant human PDGF (B chain) and a less than or equal to 1-min exposure to PDGF. Normal cellular consequences of receptor activation were also observed, including tyrosine phosphorylation of a 42-kDa protein and serine phosphorylation of ribosomal protein S6. Furthermore, PDGF was mitogenic for these cells. Microvascular endothelial cells play a central role in neovascularization required for wound healing and solid tumor growth. Thus, the discovery of functional PDGF receptors on human microvascular endothelial cells suggests a direct role for PDGF in this process.
Beitz
J G
JG
Department of Medicine, Roger Williams General Hospital, Providence, RI.
Kim
I S
IS
Calabresi
P
P
Frackelton
A R
AR
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008833:Microcirculation; D008970:Molecular Weight; D010750:Phosphoproteins / Q000302:isolation & purification; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D012867:Skin / Q000166:cytology
D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor