T Horiuchi and PF Weller
Department of Medicine, Harvard Thorndike Laboratories, Boston, Massachusetts, USA.

Vascular endothelial growth factor (VEGF) is a pleiotropic polypeptide that mediates endothelial-cell-specific responses such as induction of proliferation and vascular leakage. We examined the expression of VEGF messenger RNA (mRNA) and protein by human eosinophils in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5). Immunoreactive VEGF protein was detected in freshly isolated eosinophils by immunocytochemistry. Eosinophils spontaneously released VEGF protein in culture medium, and this release was upregulated by GM-CSF or IL-5. Freshly isolated eosinophils constitutively expressed VEGF mRNA. Although incubation of eosinophils in culture medium reduced steady-state VEGF mRNA levels, eosinophil VEGF mRNA levels were enhanced by GM-CSF and IL-5, and this enhancement was blocked by the transcription inhibitor actinomycin D. Analysis of alternatively spliced mRNA species revealed that eosinophils contained transcripts mainly encoding for the 121- and 165-amino-acid forms of VEGF. VEGF mRNA expression and VEGF release in cytokine-stimulated eosinophils were significantly reduced by treatment with a glucocorticosteroid, a protein-tyrosine kinase inhibitor, or a protein kinase C inhibitor. Cytokine-activated eosinophils may be an important source of a vascular permeability factor, namely VEGF, thus contributing to tissue edema formation at sites of allergic inflammation.

This article has been cited by other articles:

				K. S. Lee, S. R. Kim, S. J. Park, K. H. Min, K. Y. Lee, Y. H. Choe, S. Y. Park, O. H. Chai, X. Zhang, C. H. Song, et al. Mast Cells Can Mediate Vascular Permeability through Regulation of the PI3K-HIF-1{alpha}-VEGF Axis Am. J. Respir. Crit. Care Med., October 15, 2008; 178(8): 787 - 797. [Abstract] [Full Text] [PDF]

				C. Tefe-Silva, D. I. Souza, M. T. Ueta, E. M. Floriano, L. H. Faccioli, and S. G. Ramos Interference of Dexamethasone in the Pulmonary Cycle of Strongyloides venezuelensis in Rats Am J Trop Med Hyg, October 1, 2008; 79(4): 571 - 578. [Abstract] [Full Text] [PDF]

				A.H. Nissim Ben Efraim and F. Levi-Schaffer Review: Tissue remodeling and angiogenesis in asthma: the role of the eosinophil Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 163 - 171. [Abstract] [PDF]

				C. S. Restrepo, J. A. Carrillo, S. Martinez, P. Ojeda, A. L. Rivera, and A. Hatta Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations RadioGraphics, July 1, 2007; 27(4): 941 - 956. [Abstract] [Full Text] [PDF]

				H. Kanazawa, S. Nomura, and K. Asai Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients Chest, April 1, 2007; 131(4): 1035 - 1041. [Abstract] [Full Text] [PDF]

				K. S. Lee, K. H. Min, S. R. Kim, S. J. Park, H. S. Park, G. Y. Jin, and Y. C. Lee Vascular Endothelial Growth Factor Modulates Matrix Metalloproteinase-9 Expression in Asthma Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 161 - 170. [Abstract] [Full Text] [PDF]

				K. S. Lee, S. R. Kim, S. J. Park, H. K. Lee, H. S. Park, K. H. Min, S. M. Jin, and Y. C. Lee Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Reduces Vascular Endothelial Growth Factor Expression in Allergen-Induced Airway Inflammation Mol. Pharmacol., June 1, 2006; 69(6): 1829 - 1839. [Abstract] [Full Text] [PDF]

				J. Cao, C. L. Cetrulo, and T. C. Theoharides Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway Mol. Pharmacol., March 1, 2006; 69(3): 998 - 1006. [Abstract] [Full Text] [PDF]

				A. M. O. Abdel-Rahman, S. A. F. El-Sahrigy, and S. I. Bakr A comparative study of two angiogenic factors: vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack. Chest, February 1, 2006; 129(2): 266 - 271. [Abstract] [Full Text] [PDF]

				H. Mitsuyama, W. Matsuyama, J. Iwakawa, I. Higashimoto, M. Watanabe, M. Osame, and K. Arimura Increased serum vascular endothelial growth factor level in churg-strauss syndrome. Chest, February 1, 2006; 129(2): 407 - 411. [Abstract] [Full Text] [PDF]

				A J Knox, J Stocks, and A Sutcliffe Angiogenesis and vascular endothelial growth factor in COPD Thorax, February 1, 2005; 60(2): 88 - 89. [Full Text] [PDF]

				B Heryanto, J E Girling, and P A W Rogers Intravascular neutrophils partially mediate the endometrial endothelial cell proliferative response to oestrogen in ovariectomised mice Reproduction, May 1, 2004; 127(5): 613 - 620. [Abstract] [Full Text] [PDF]

				C. Feistritzer, N. C. Kaneider, D. H. Sturn, B. A. Mosheimer, C. M. Kahler, and C. J. Wiedermann Expression and Function of the Vascular Endothelial Growth Factor Receptor FLT-1 in Human Eosinophils Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 729 - 735. [Abstract] [Full Text] [PDF]

				T. Usui, S. Ishida, K. Yamashiro, Y. Kaji, V. Poulaki, J. Moore, T. Moore, S. Amano, Y. Horikawa, D. Dartt, et al. VEGF164(165) as the Pathological Isoform: Differential Leukocyte and Endothelial Responses through VEGFR1 and VEGFR2 Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 368 - 374. [Abstract] [Full Text] [PDF]

				R. Paine III, S. E. Wilcoxen, S. B. Morris, C. Sartori, C. E. O. Baleeiro, M. A. Matthay, and P. J. Christensen Transgenic Overexpression of Granulocyte Macrophage-Colony Stimulating Factor in the Lung Prevents Hyperoxic Lung Injury Am. J. Pathol., December 1, 2003; 163(6): 2397 - 2406. [Abstract] [Full Text]

				B.A. Roopa, A. Loganath, and K. Singh The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium Hum. Reprod., September 1, 2003; 18(9): 1809 - 1819. [Abstract] [Full Text] [PDF]

				D H Strong, J Y Westcott, J A Biller, J L Morrison, R M Effros, and J P Maloney Eosinophilic "empyema" associated with crack cocaine use Thorax, September 1, 2003; 58(9): 823 - 824. [Abstract] [Full Text] [PDF]

				G. Vento, P. G. Matassa, E. Capoluongo, L. Tortorolo, C. Romagnoli, F. Ameglio, P. Lassus, and S. Andersson Glucocorticoids in Preterm Infants and Discrepancies of Vascular Endothelial Growth Factor Am. J. Respir. Crit. Care Med., August 15, 2003; 168(4): 501 - 502. [Full Text]

				Y. Nishigaki, S. Fujiuchi, Y. Yamazaki, H. Matsumoto, A. Takeda, Y. Fujita, K. Okamoto, T. Fujikane, T. Shimizu, and K. Kikuchi Increased vascular endothelial growth factor in acute eosinophilic pneumonia Eur. Respir. J., May 1, 2003; 21(5): 774 - 778. [Abstract] [Full Text] [PDF]

				W. Duan, I. C. Kuo, S. Selvarajan, K. Y. Chua, B. H. Bay, and W. S. F. Wong Antiinflammatory Effects of Genistein, a Tyrosine Kinase Inhibitor, on a Guinea Pig Model of Asthma Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 185 - 192. [Abstract] [Full Text] [PDF]

				S. Phipps, S. Ying, A. Wangoo, Y.-E. Ong, F. Levi-Schaffer, and A. B. Kay The Relationship Between Allergen-Induced Tissue Eosinophilia and Markers of Repair and Remodeling in Human Atopic Skin J. Immunol., October 15, 2002; 169(8): 4604 - 4612. [Abstract] [Full Text] [PDF]

				S. A. Woods, C. J. McGlade, and A. Guha Phosphatidylinositol 3'-kinase and MAPK/ERK kinase 1/2 differentially regulate expression of vascular endothelial growth factor in human malignant astrocytoma cells Neuro-oncol, October 1, 2002; 4(4): 242 - 252. [Abstract] [PDF]

				Y. C. Lee, Y.-G. Kwak, and C. H. Song Contribution of Vascular Endothelial Growth Factor to Airway Hyperresponsiveness and Inflammation in a Murine Model of Toluene Diisocyanate-Induced Asthma J. Immunol., April 1, 2002; 168(7): 3595 - 3600. [Abstract] [Full Text] [PDF]

				H. Kobayashi, G. J. Gleich, J. H. Butterfield, and H. Kita Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli Blood, March 15, 2002; 99(6): 2214 - 2220. [Abstract] [Full Text] [PDF]

				A. M. Joussen, V. Poulaki, W. Qin, B. Kirchhof, N. Mitsiades, S. J. Wiegand, J. Rudge, G. D. Yancopoulos, and A. P. Adamis Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo Am. J. Pathol., February 1, 2002; 160(2): 501 - 509. [Abstract] [Full Text] [PDF]

				T. Qaum, Q. Xu, A. M. Joussen, M. W. Clemens, W. Qin, K. Miyamoto, H. Hassessian, S. J. Wiegand, J. Rudge, G. D. Yancopoulos, et al. VEGF-initiated Blood-Retinal Barrier Breakdown in Early Diabetes Invest. Ophthalmol. Vis. Sci., September 1, 2001; 42(10): 2408 - 2413. [Abstract] [Full Text] [PDF]

				M. Song, S. Ramaswamy, S. Ramachandran, L. C. Flowers, I. R. Horowitz, J. A. Rock, and S. Parthasarathy Angiogenic role for glycodelin in tumorigenesis PNAS, July 13, 2001; (2001) 151151198. [Abstract] [Full Text] [PDF]

				M. Clauss, C. Sunderkotter, B. Sveinbjornsson, S. Hippenstiel, A. Willuweit, M. Marino, E. Haas, R. Seljelid, P. Scheurich, N. Suttorp, et al. A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability Blood, March 1, 2001; 97(5): 1321 - 1329. [Abstract] [Full Text] [PDF]

				C. G. Lee, H. J. Yoon, Z. Zhu, H. Link, Z. Wang, J. M. Gwaltney Jr., M. Landry, and J. A. Elias Respiratory Syncytial Virus Stimulation of Vascular Endothelial Cell Growth Factor/Vascular Permeability Factor Am. J. Respir. Cell Mol. Biol., November 1, 2000; 23(5): 662 - 669. [Abstract] [Full Text]

				Y. Moromizato, S. Stechschulte, K. Miyamoto, T. Murata, A. Tsujikawa, A. M. Joussen, and A. P. Adamis CD18 and ICAM-1-Dependent Corneal Neovascularization and Inflammation after Limbal Injury Am. J. Pathol., October 1, 2000; 157(4): 1277 - 1281. [Abstract] [Full Text] [PDF]

				S. Ali, J. Kaur, and K. D. Patel Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation Am. J. Pathol., July 1, 2000; 157(1): 313 - 321. [Abstract] [Full Text] [PDF]

				K. Miyamoto, S. Khosrof, S.-E. Bursell, Y. Moromizato, L. P. Aiello, Y. Ogura, and A. P. Adamis Vascular Endothelial Growth Factor (VEGF)-Induced Retinal Vascular Permeability Is Mediated by Intercellular Adhesion Molecule-1 (ICAM-1) Am. J. Pathol., May 1, 2000; 156(5): 1733 - 1739. [Abstract] [Full Text] [PDF]

				J. M. Wood, G. Bold, E. Buchdunger, R. Cozens, S. Ferrari, J. Frei, F. Hofmann, J. Mestan, H. Mett, T. O’Reilly, et al. PTK787/ZK 222584, a Novel and Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, Impairs Vascular Endothelial Growth Factor-induced Responses and Tumor Growth after Oral Administration Cancer Res., April 1, 2000; 60(8): 2178 - 2189. [Abstract] [Full Text]

				P. M. Becker, A. Alcasabas, A. Y. Yu, G. L. Semenza, and T. E. Bunton Oxygen-Independent Upregulation of Vascular Endothelial Growth Factor and Vascular Barrier Dysfunction during Ventilated Pulmonary Ischemia in Isolated Ferret Lungs Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 272 - 279. [Abstract] [Full Text]

				M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]

				T. M. Lau, B. Affandi, and P. A.W. Rogers The effects of levonorgestrel implants on vascular endothelial growth factor expression in the endometrium Mol. Hum. Reprod., January 1, 1999; 5(1): 57 - 63. [Abstract] [Full Text] [PDF]

				C. G. Kevil, D. K. Payne, E. Mire, and J. S. Alexander Vascular Permeability Factor/Vascular Endothelial Cell Growth Factor-mediated Permeability Occurs through Disorganization of Endothelial Junctional Proteins J. Biol. Chem., June 12, 1998; 273(24): 15099 - 15103. [Abstract] [Full Text] [PDF]

				M. Song, S. Ramaswamy, S. Ramachandran, L. C. Flowers, I. R. Horowitz, J. A. Rock, and S. Parthasarathy Angiogenic role for glycodelin in tumorigenesis PNAS, July 31, 2001; 98(16): 9265 - 9270. [Abstract] [Full Text] [PDF]