| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 148, 439-451, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
CE Alpers, CL Davis, D Barr, CL Marsh and KL Hudkins
Department of Pathology, University of Washington, Seattle 98195, USA.
Platelet-derived growth factor (PDGF) exists as a dimer composed of two homologous but distinct peptides termed PDGF-A and -B chains, and may exist as AA, AB, and BB isoforms. The PDGF-B chain has been implicated as a mediator of renal vascular rejection by virtue of up-regulated expression of its receptor, PDGF beta-receptor, in affected arteries. A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet- derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Circ Res 1994, 75:410), but no studies of this molecule in human renal allograft injury have been reported to date. We used two polyclonal antisera to detect expression of PDGF-A chain and one monoclonal antibody to detect PDGF-B chain by immunohistochemistry in fixed, paraffin-embedded tissue from 1) normal adult kidneys, 2) a series of renal transplant biopsies chosen to emphasize features of vascular rejection, and 3) allograft nephrectomies. Immunohistochemistry was correlated with in situ hybridization on adjacent, formalin fixed tissue sections from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA. PDGF-A chain is widely expressed by medial smooth muscle cells of normal and rejecting renal arterial vessels of all sizes by immunohistochemistry and in situ hybridization. PDGF-A chain is also expressed by a population of smooth muscle cells (shown by double immunolabeling with an antibody to alpha-smooth muscle actin) comprising the intima in chronic vascular rejection. In arteries demonstrating acute rejection, up-regulated expression of PDGF-A chain by endothelial cells was detected by both immunohistochemistry and in situ hybridization. In contrast, PDGF-B chain was identified principally in infiltrating monocytes within the rejecting arteries, similar to its localization in infiltrating monocytes in human atherosclerosis. Although less prominent than the case for PDGF-A chain, PDGF-B chain also was present in medial and intimal smooth muscle cells in both rejecting and nonrejecting renal arteries. PDGF-A and -B chains have now been localized at both the mRNA and protein levels to the intimal proliferative lesions of vascular rejection. These peptides, which are known stimuli for smooth muscle cell migration and proliferation in experimental vascular injury, may have similar stimulatory effects on smooth muscle cells in an autocrine and/or paracrine manner to promote further intimal expansion and lesion progression in this form of human vasculopathy.
This article has been cited by other articles:
 |
|
 |
|
  S. Taneda, K. L. Hudkins, A. S. Muhlfeld, J. Kowalewska, J. W. Pippin, S. J. Shankland, and C. E. Alpers Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 243 - 251. [Full Text] [PDF]
|
|
|
|
|
|
J. Floege, F. Eitner, and C. E. Alpers A New Look at Platelet-Derived Growth Factor in Renal Disease J. Am. Soc. Nephrol., January 1, 2008; 19(1): 12 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Helantera, R. Loginov, P. Koskinen, T. Tornroth, C. Gronhagen-Riska, and I. Lautenschlager Persistent cytomegalovirus infection is associated with increased expression of TGF-{beta}1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney allografts Nephrol. Dial. Transplant., April 1, 2005; 20(4): 790 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Taneda, K. L. Hudkins, S. Topouzis, D. G. Gilbertson, V. Ophascharoensuk, L. Truong, R. J. Johnson, and C. E. Alpers Obstructive Uropathy in Mice and Humans: Potential Role for PDGF-D in the Progression of Tubulointerstitial Injury J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2544 - 2555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Eitner, T. Ostendorf, M. Kretzler, C. D. Cohen, U. Eriksson, H.-J. Grone, and J. Floege PDGF-C Expression in the Developing and Normal Adult Human Kidney and in Glomerular Diseases J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1145 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Vail, R. H. Pierce, and N. Fausto Bcl-2 Delays and Alters Hepatic Carcinogenesis Induced by Transforming Growth Factor {{alpha}} Cancer Res., January 1, 2001; 61(2): 594 - 601. [Abstract] [Full Text]
|
|
|
|
|
|
F. EITNER, Y. CUI, K. L. HUDKINS, M. B. STOKES, S. SEGERER, M. MACK, P. L. LEWIS, A. A. ABRAHAM, D. SCHLÖNDORFF, G. GALLO, et al. Chemokine Receptor CCR5 and CXCR4 Expression in HIV-Associated Kidney Disease J. Am. Soc. Nephrol., May 1, 2000; 11(5): 856 - 867. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Eitner, Y. Cui, G. Grouard-Vogel, K. L. Hudkins, A. Schmidt, T. Birkebak, M. B. Agy, S.-L. Hu, W. R. Morton, D. M. Anderson, et al. Rapid Shift from Virally Infected Cells to Germinal Center-Retained Virus after HIV-2 Infection of Macaques Am. J. Pathol., April 1, 2000; 156(4): 1197 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Heldin and B. Westermark Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor Physiol Rev, October 1, 1999; 79(4): 1283 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Eitner, Y. Cui, K. L. Hudkins, A. Schmidt, T. Birkebak, M. B. Agy, S.-L. Hu, W. R. Morton, D. M. Anderson, and C. E. Alpers Thrombotic Microangiopathy in the HIV-2-Infected Macaque Am. J. Pathol., August 1, 1999; 155(2): 649 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Totani, A. Cumashi, A. Piccoli, and R. Lorenzet Polymorphonuclear Leukocytes Induce PDGF Release From IL-1ß–Treated Endothelial Cells : Role of Adhesion Molecules and Serine Proteases Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1534 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Lemstrom and P. K. Koskinen Expression and Localization of Platelet-Derived Growth Factor Ligand and Receptor Protein During Acute and Chronic Rejection of Rat Cardiac Allografts Circulation, August 19, 1997; 96(4): 1240 - 1249. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
