|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 December 2000, Vol. 96, No. 12, pp. 3801-3808
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Ligation of CD40 induces the expression of vascular endothelial
growth factor by endothelial cells and monocytes and promotes
angiogenesis in vivo
Michael Melter,
Marlies E. J. Reinders,
Masayuki Sho,
Soumitro Pal,
Christopher Geehan,
Mark D. Denton,
Debabrata Mukhopadhyay, and
David M. Briscoe
From The Division of Nephrology, Department of
Medicine, Children's Hospital; the Department of Pediatrics, Harvard
Medical School; and the Department of Pathology, Beth Israel Deaconess
Medical Center, Boston, MA.
This study addresses a mechanism by which lymphocytes may promote
vascular endothelial growth factor (VEGF) expression and angiogenesis
in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA
(mRNA) by reverse transcription polymerase chain reaction and
ribonuclease protection assay with little or no change in expression
following activation by cytokines, including tumor necrosis factor- ,
interleukin (IL)-1, interferon  , or IL-4. In contrast, treatment of
HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a
marked dose-dependent induction of VEGF mRNA (approximately 4-fold),
which peaked between 1 and 5 hours post-stimulation. Transient
transfection of HUVECs was performed with a luciferase reporter
construct under the control of the human VEGF promoter. Treatment of
transfected HUVECs with sCD40L was found to enhance luciferase activity
(approximately 4-fold) compared with controls, similar to the relative
fold induction in mRNA expression in parallel cultures. Thus,
CD40-dependent VEGF expression was a result of transcriptional control
mechanisms. Treatment of HUVECs with sCD40L was also found to function
in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found
following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and
nude mice induced VEGF expression and marked angiogenesis in vivo.
Taken together, these findings are consistent with a function for
CD40L-CD40 interactions in VEGF-induced angiogenesis and define a
mechanistic link between the immune response and angiogenesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein
Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions
Cardiovasc Res,
May 1, 2008;
78(2):
257 - 264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. G. Spagnoli, E. Bonanno, G. Sangiorgi, and A. Mauriello
Role of Inflammation in Atherosclerosis
J. Nucl. Med.,
November 1, 2007;
48(11):
1800 - 1815.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S Danese, F Scaldaferri, S Vetrano, T Stefanelli, C Graziani, A Repici, R Ricci, G Straface, A Sgambato, A Malesci, et al.
Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease
Gut,
September 1, 2007;
56(9):
1248 - 1256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Chiodoni, M. Iezzi, C. Guiducci, S. Sangaletti, I. Alessandrini, C. Ratti, F. Tiboni, P. Musiani, D. N. Granger, and M. P. Colombo
Triggering CD40 on endothelial cells contributes to tumor growth
J. Exp. Med.,
October 30, 2006;
203(11):
2441 - 2450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bergmann and P. P. Pandolfi
Giving blood: a new role for CD40 in tumorigenesis
J. Exp. Med.,
October 30, 2006;
203(11):
2409 - 2412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E.J. Reinders, T. J. Rabelink, and D. M. Briscoe
Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection
J. Am. Soc. Nephrol.,
April 1, 2006;
17(4):
932 - 942.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Boulday, Z. Haskova, M. E. J. Reinders, S. Pal, and D. M. Briscoe
Vascular Endothelial Growth Factor-Induced Signaling Pathways in Endothelial Cells That Mediate Overexpression of the Chemokine IFN-{gamma}-Inducible Protein of 10 kDa In Vitro and In Vivo.
J. Immunol.,
March 1, 2006;
176(5):
3098 - 3107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-i. Tsuchihashi, B. Ke, F. Kaldas, E. Flynn, R. W. Busuttil, D. M. Briscoe, and J. W. Kupiec-Weglinski
Vascular Endothelial Growth Factor Antagonist Modulates Leukocyte Trafficking and Protects Mouse Livers against Ischemia/Reperfusion Injury
Am. J. Pathol.,
February 1, 2006;
168(2):
695 - 705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Virmani, F. D. Kolodgie, A. P. Burke, A. V. Finn, H. K. Gold, T. N. Tulenko, S. P. Wrenn, and J. Narula
Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage
Arterioscler. Thromb. Vasc. Biol.,
October 1, 2005;
25(10):
2054 - 2061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Laxmanan, D. Datta, C. Geehan, D. M. Briscoe, and S. Pal
CD40: A Mediator of Pro- and Anti-Inflammatory Signals in Renal Tubular Epithelial Cells
J. Am. Soc. Nephrol.,
September 1, 2005;
16(9):
2714 - 2723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Hamada, K. Kuwano, M. Yamada, N. Hagimoto, K. Hiasa, K. Egashira, N. Nakashima, T. Maeyama, M. Yoshimi, and Y. Nakanishi
Anti-Vascular Endothelial Growth Factor Gene Therapy Attenuates Lung Injury and Fibrosis in Mice
J. Immunol.,
July 15, 2005;
175(2):
1224 - 1231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ishikawa, T. Vowinkel, K. Y. Stokes, T. V. Arumugam, G. Yilmaz, A. Nanda, and D. N. Granger
CD40/CD40 Ligand Signaling in Mouse Cerebral Microvasculature After Focal Ischemia/Reperfusion
Circulation,
April 5, 2005;
111(13):
1690 - 1696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Tsutsumi-Miyahara, K-H Sonoda, K Egashira, M Ishibashi, H Qiao, T Oshima, T Murata, M Miyazaki, I F Charo, S Hamano, et al.
The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation
Br. J. Ophthalmol.,
September 1, 2004;
88(9):
1217 - 1222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Lapchak, M. Melter, S. Pal, J. A. Flaxenburg, C. Geehan, M. H. Frank, D. Mukhopadhyay, and D. M. Briscoe
CD40-induced transcriptional activation of vascular endothelial growth factor involves a 68-bp region of the promoter containing a CpG island
Am J Physiol Renal Physiol,
September 1, 2004;
287(3):
F512 - F520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kinnaird, E. Stabile, M. S. Burnett, and S. E. Epstein
Bone Marrow-Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences
Circ. Res.,
August 20, 2004;
95(4):
354 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S Danese, M Sans, and C Fiocchi
The CD40/CD40L costimulatory pathway in inflammatory bowel disease
Gut,
July 1, 2004;
53(7):
1035 - 1043.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Flaxenburg, M. Melter, P. H. Lapchak, D. M. Briscoe, and S. Pal
The CD40-Induced Signaling Pathway in Endothelial Cells Resulting in the Overexpression of Vascular Endothelial Growth Factor Involves Ras and Phosphatidylinositol 3-Kinase
J. Immunol.,
June 15, 2004;
172(12):
7503 - 7509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W. Henderson, R. Ruhl, P. Lewis, M. Bentley, J. A. Nelson, and A. V. Moses
Human Immunodeficiency Virus (HIV) Type 1 Vpu Induces the Expression of CD40 in Endothelial Cells and Regulates HIV-Induced Adhesion of B-Lymphoma Cells
J. Virol.,
May 1, 2004;
78(9):
4408 - 4420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ottaiano, A. De Chiara, F. Perrone, G. Botti, F. Fazioli, V. De Rosa, N. Mozzillo, V. Ravo, B. Morrica, C. Gallo, et al.
Prognostic Value of CD40 in Adult Soft Tissue Sarcomas
Clin. Cancer Res.,
April 15, 2004;
10(8):
2824 - 2831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Roselli, T. C. Mineo, S. Basili, F. Martini, S. Mariotti, S. Aloe, G. Del Monte, V. Ambrogi, A. Spila, R. Palmirotta, et al.
Soluble CD40 Ligand Plasma Levels in Lung Cancer
Clin. Cancer Res.,
January 15, 2004;
10(2):
610 - 614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Raza, G. N. Fuller, C. H. Rhee, S. Huang, K. Hess, W. Zhang, and R. Sawaya
Identification of Necrosis-Associated Genes in Glioblastoma by cDNA Microarray Analysis
Clin. Cancer Res.,
January 1, 2004;
10(1):
212 - 221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Russo, B. Bussolati, I. Deambrosis, F. Mariano, and G. Camussi
Platelet-Activating Factor Mediates CD40-Dependent Angiogenesis and Endothelial-Smooth Muscle Cell Interaction
J. Immunol.,
November 15, 2003;
171(10):
5489 - 5497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Friedlander, C. L. Delaune, J. M. Abadie, M. Toups, J. LaCour, L. Marrero, Q. Zhong, and J. K. Kolls
Efficacy of CD40 Ligand Gene Therapy in Malignant Mesothelioma
Am. J. Respir. Cell Mol. Biol.,
September 1, 2003;
29(3):
321 - 330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. J. Reinders, M. Sho, S. W. Robertson, C. S. Geehan, and D. M. Briscoe
Proangiogenic Function of CD40 Ligand-CD40 Interactions
J. Immunol.,
August 1, 2003;
171(3):
1534 - 1541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Tsutsumi, K.-H. Sonoda, K. Egashira, H. Qiao, T. Hisatomi, S. Nakao, M. Ishibashi, I. F. Charo, T. Sakamoto, T. Murata, et al.
The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization
J. Leukoc. Biol.,
July 1, 2003;
74(1):
25 - 32.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.D. Garlichs, S. Kozina, S. Fateh-Moghadam, B. Tomandl, C. Stumpf, S. Eskafi, D. Raaz, A. Schmeisser, A. Yilmaz, J. Ludwig, et al.
Upregulation of CD40-CD40 Ligand (CD154) in Patients With Acute Cerebral Ischemia
Stroke,
June 1, 2003;
34(6):
1412 - 1418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Deregibus, S. Buttiglieri, S. Russo, B. Bussolati, and G. Camussi
CD40-dependent Activation of Phosphatidylinositol 3-Kinase/Akt Pathway Mediates Endothelial Cell Survival and in Vitro Angiogenesis
J. Biol. Chem.,
May 9, 2003;
278(20):
18008 - 18014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-T. Tai, K. Podar, N. Mitsiades, B. Lin, C. Mitsiades, D. Gupta, M. Akiyama, L. Catley, T. Hideshima, N. C. Munshi, et al.
CD40 induces human multiple myeloma cell migration via phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling
Blood,
April 1, 2003;
101(7):
2762 - 2769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kiriakidis, E. Andreakos, C. Monaco, B. Foxwell, M. Feldmann, and E. Paleolog
VEGF expression in human macrophages is NF-{kappa}B-dependent: studies using adenoviruses expressing the endogenous NF-{kappa}B inhibitor I{kappa}B{alpha} and a kinase-defective form of the I{kappa}B kinase 2
J. Cell Sci.,
February 15, 2003;
116(4):
665 - 674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Urbich, E. Dernbach, A. Aicher, A. M. Zeiher, and S. Dimmeler
CD40 Ligand Inhibits Endothelial Cell Migration by Increasing Production of Endothelial Reactive Oxygen Species
Circulation,
August 20, 2002;
106(8):
981 - 986.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Franz Alber, J. Dulak, M. Frick, W. Dichtl, S. Paul Schwarzacher, O. Pachinger, and F. Weidinger
Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease
J. Am. Coll. Cardiol.,
June 19, 2002;
39(12):
1951 - 1955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Monaco, E. Andreakos, S. Young, M. Feldmann, and E. Paleolog
T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor
J. Leukoc. Biol.,
April 1, 2002;
71(4):
659 - 668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-T. Tai, K. Podar, D. Gupta, B. Lin, G. Young, M. Akiyama, and K. C. Anderson
CD40 activation induces p53-dependent vascular endothelial growth factor secretion in human multiple myeloma cells
Blood,
February 15, 2002;
99(4):
1419 - 1427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Schonbeck and P. Libby
CD40 Signaling and Plaque Instability
Circ. Res.,
December 7, 2001;
89(12):
1092 - 1103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Garlichs, S. John, A. Schmei{beta}er, S. Eskafi, C. Stumpf, M. Karl, M. Goppelt-Struebe, R. Schmieder, and W. G. Daniel
Upregulation of CD40 and CD40 Ligand (CD154) in Patients With Moderate Hypercholesterolemia
Circulation,
November 13, 2001;
104(20):
2395 - 2400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
