© 1997 American Heart Association, Inc.
Articles |
Platelet-Derived Growth Factor ß-Receptors Can Both Promote and Inhibit Chemotaxis in Human Vascular Smooth Muscle Cells
From the Department of Clinical Pharmacology, Imperial College School of Medicine at St Mary's, London, UK.
Correspondence to Dr Gerard Clunn, Department of Clinical Pharmacology, Imperial College School of Medicine at St Mary's, South Wharf Rd, Paddington, London, W2 1NY, UK. E-mail g.clunn{at}ic.ac.uk
Abstract The effect of the three platelet-derived growth
factor (PDGF) isoforms AA, AB, and BB on migration was investigated in
cultured human saphenous vein smooth muscle cells. The modified Boyden
chamber technique yielded efficacies BB>>AB, AA=0. However,
the BB concentration-response relationship displayed a pronounced peak,
occurring between 1 and 10 ng/mL, with no response above this range.
Checkerboard analysis showed that the promotion of migration at
low concentrations was chemotactic in nature but that the downturn was
independent of gradient. Furthermore, at high concentrations BB was
able to prevent chemotaxis induced by fetal calf serum and epidermal
growth factor (EGF). Experiments using low concentrations of BB in
combination with high concentrations of AA to saturate PDGF
-receptors in the presence and absence of a neutralizing antibody to
-receptors revealed that -receptor activation induced partial
inhibition of chemotaxis but this did not account for the inhibition of
migration by high concentrations of BB. Despite possessing no
significant chemotactic action itself, high concentrations of the AB
isoform completely inhibited BB induced chemotaxis. Taken together
these results suggest that the chemotactic signal induced by PDGF is
dominated by PDGF ß-receptors and switches from positive at low
concentrations to negative at higher concentrations. Stimulation of DNA
synthesis by the three isoforms (as measured by [3H]
thymidine incorporation) yielded saturable responses for the AB and BB
isoforms, with similar efficacy and weak or no response for the AA
isoform. Concentration-dependent patterns of tyrosine
phosphorylation of certain proteins mirrored the form
of the chemotactic response and suggest one possible underlying
regulatory mechanism to account for the disparity between PDGF-induced
chemotaxis and DNA synthesis.
Key Words: vascular smooth muscle • platelet-derived growth factor • chemotaxis • tyrosine phosphorylation
This article has been cited by other articles:
 |
|
 |
|
  D. Faraone, M. S. Aguzzi, G. Ragone, K. Russo, M. C. Capogrossi, and A. Facchiano Heterodimerization of FGF-receptor 1 and PDGF-receptor-{alpha}: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells Blood, March 1, 2006; 107(5): 1896 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Koutsouki, C. A. Beeching, S. C. Slater, O. W. Blaschuk, G. B. Sala-Newby, and S. J. George N-Cadherin-Dependent Cell-Cell Contacts Promote Human Saphenous Vein Smooth Muscle Cell Survival Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 982 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Garanich, M. Pahakis, and J. M. Tarbell Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2244 - H2252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Hunton, W. G. Barnes, J. Kim, X.-R. Ren, J. D. Violin, E. Reiter, G. Milligan, D. D. Patel, and R. J. Lefkowitz {beta}-Arrestin 2-Dependent Angiotensin II Type 1A Receptor-Mediated Pathway of Chemotaxis Mol. Pharmacol., April 1, 2005; 67(4): 1229 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Lymn, M. K. Patel, G. F. Clunn, S. J. Rao, K. L. Gallagher, and A. D. Hughes Thrombospondin-1 differentially induces chemotaxis and DNA synthesis of human venous smooth muscle cells at the receptor-binding level J. Cell Sci., November 15, 2002; 115(22): 4353 - 4360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. De Marchis, D. Ribatti, C. Giampietri, A. Lentini, D. Faraone, M. Scoccianti, M. C. Capogrossi, and A. Facchiano Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor Blood, March 15, 2002; 99(6): 2045 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Buetow, J. R. Crosby, W. E. Kaminski, R. K. Ramachandran, P. Lindahl, P. Martin, C. Betsholtz, R. A. Seifert, E. W. Raines, and D. F. Bowen-Pope Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization Am. J. Pathol., November 1, 2001; 159(5): 1869 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ma, D. P. Mason, and D. B. Young Inhibition of Vascular Smooth Muscle Cell Migration by Elevation of Extracellular Potassium Concentration Hypertension, April 1, 2000; 35(4): 948 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Facchiano, F De Marchis, E Turchetti, F Facchiano, M Guglielmi, A Denaro, R Palumbo, M Scoccianti, and M. Capogrossi The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor J. Cell Sci., January 8, 2000; 113(16): 2855 - 2863. [Abstract] [PDF]
|
|
|
|
|
|
J. S. Lymn, S. J. Rao, G. F. Clunn, K. L. Gallagher, C. O'Neil, N. T. Thompson, and A. D. Hughes Phosphatidylinositol 3-Kinase and Focal Adhesion Kinase Are Early Signals in the Growth Factor–Like Responses to Thrombospondin-1 Seen in Human Vascular Smooth Muscle Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2133 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, C. S. Facemire, A. J. Banes, and J. E. Faber Different alpha -adrenoceptors mediate migration of vascular smooth muscle cells and adventitial fibroblasts in vitro Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2364 - H2370. [Abstract] [Full Text] [PDF]
|
|