This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Powell, P. P. Articles by Jones, R. C. Search for Related Content PubMed PubMed Citation Articles by Powell, P. P. Articles by Jones, R. C.

American Journal of Pathology, Vol 143, 784-793, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Eosinophils expressing heparin-binding EGF-like growth factor mRNA localize around lung microvessels in pulmonary hypertension

PP Powell, M Klagsbrun, JA Abraham and RC Jones
Department of Anesthesia, Massachusetts General Hospital, Boston.

In pulmonary hypertension, induced in rats breathing high oxygen at normobaric pressure, vascular cell hypertrophy and hyperplasia thicken the walls of lung microvessels (15-100 microns in diameter). Over a 28- day time course, new contractile cells develop from intimal precursor smooth muscle cells, which include intermediate cells and interstitial fibroblasts. Cell labeling studies in vivo have shown that these cells proliferate more than other vascular cells and that most of this activity occurs between 4 and 7 days of hyperoxia. The growth factors responsible for this proliferation are unknown. In the present study, we investigate the expression of mRNA for the epidermal growth factor (EGF)-related protein, heparin-binding EGF-like growth factor (HB-EGF), a newly discovered mitogen for fibroblasts and smooth muscle cells. Northern analysis shows HB-EGF mRNA levels to be low in normal lung but increased 100-fold by day 7 of hyperoxia. In situ hybridization identifies a select group of cells expressing HB-EGF mRNA. In normal lung, hybridizing cells are randomly distributed in the alveolar wall and space. By day 7, they increase in number and cluster around the microvessels. Histochemical techniques identify cells expressing HB-EGF mRNA as eosinophils.

This article has been cited by other articles:

				J. E. Faber, C. L. Szymeczek, S. Cotecchia, S. A. Thomas, A. Tanoue, G. Tsujimoto, and H. Zhang {alpha}1-Adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2316 - H2323. [Abstract] [Full Text] [PDF]

				J. E. Faber, C. L. Szymeczek, S. S. Salvi, and H. Zhang Enhanced {alpha}1-adrenergic trophic activity in pulmonary artery of hypoxic pulmonary hypertensive rats Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2272 - H2281. [Abstract] [Full Text] [PDF]

				J. Liu, C. B. Rich, J. A. Buczek-Thomas, M. A. Nugent, M. P. Panchenko, and J. A. Foster Heparin-binding EGF-like growth factor regulates elastin and FGF-2 expression in pulmonary fibroblasts Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1106 - L1115. [Abstract] [Full Text] [PDF]

				J. L. Ingram, A. B. Rice, J. Santos, B. Van Houten, and J. C. Bonner Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L774 - L782. [Abstract] [Full Text] [PDF]

				M. Levi, L. Moons, A. Bouche, S. D. Shapiro, D. Collen, and P. Carmeliet Deficiency of Urokinase-Type Plasminogen Activator-Mediated Plasmin Generation Impairs Vascular Remodeling During Hypoxia-Induced Pulmonary Hypertension in Mice Circulation, April 17, 2001; 103(15): 2014 - 2020. [Abstract] [Full Text] [PDF]

				F. Vinante, M. Marchi, A. Rigo, P. Scapini, G. Pizzolo, and M. A. Cassatella Granulocyte-Macrophage Colony-Stimulating Factor Induces Expression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor/Diphtheria Toxin Receptor and Sensitivity to Diphtheria Toxin in Human Neutrophils Blood, November 1, 1999; 94(9): 3169 - 3177. [Abstract] [Full Text] [PDF]

				Z.'e. Gechtman, J. L. Alonso, G. Raab, D. E. Ingber, and M. Klagsbrun The Shedding of Membrane-anchored Heparin-binding Epidermal-like Growth Factor Is Regulated by the Raf/Mitogen-activated Protein Kinase Cascade and by Cell Adhesion and Spreading J. Biol. Chem., October 1, 1999; 274(40): 28828 - 28835. [Abstract] [Full Text] [PDF]

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

				R. Polosa, G. Prosperini, S.-H. Leir, S. T. Holgate, P. M. Lackie, and D. E. Davies Expression of c-erbB Receptors and Ligands in Human Bronchial Mucosa Am. J. Respir. Cell Mol. Biol., May 1, 1999; 20(5): 914 - 923. [Abstract] [Full Text]

				D. K. Madtes, A. L. Elston, R. C. Hackman, A. R. Dunn, and J. G. Clark Transforming Growth Factor-alpha Deficiency Reduces Pulmonary Fibrosis in Transgenic Mice Am. J. Respir. Cell Mol. Biol., May 1, 1999; 20(5): 924 - 934. [Abstract] [Full Text]

				F. Vinante, A. Rigo, E. Papini, M. A. Cassatella, and G. Pizzolo Heparin-Binding Epidermal Growth Factor-Like Growth Factor/Diphtheria Toxin Receptor Expression by Acute Myeloid Leukemia Cells Blood, March 1, 1999; 93(5): 1715 - 1723. [Abstract] [Full Text] [PDF]

				P. P. Powell, C.-C. Wang, H. Horinouchi, K. Shepherd, M. Jacobson, M. Lipson, and R. Jones Differential Expression of Fibroblast Growth Factor Receptors 1 to 4 and Ligand Genes in Late Fetal and Early Postnatal Rat Lung Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 563 - 572. [Abstract] [Full Text]

				M. Suzuki, G. Raab, M. A. Moses, C. A. Fernandez, and M. Klagsbrun Matrix Metalloproteinase-3 Releases Active Heparin-binding EGF-like Growth Factor by Cleavage at a Specific Juxtamembrane Site J. Biol. Chem., December 12, 1997; 272(50): 31730 - 31737. [Abstract] [Full Text] [PDF]

				T. Horiuchi and P. F. Weller Expression of Vascular Endothelial Growth Factor by Human Eosinophils: Upregulation by Granulocyte Macrophage Colony-stimulating Factor and Interleukin-5 Am. J. Respir. Cell Mol. Biol., July 1, 1997; 17(1): 70 - 77. [Abstract] [Full Text]