A Weinacker, R Ferrando, M Elliott, J Hogg, J Balmes and D Sheppard
Lung Biology Center, University of California, San Francisco 94143, USA.

We have previously identified two integrins, alpha 9 beta 1 and alpha v beta 6, from guinea pig airway epithelium. The extracellular matrix protein tenascin is a ligand for both of these receptors, and fibronectin is also a ligand for alpha v beta 6. In the present study, we used immunohistochemistry to examine the expression and spatial distribution of the alpha 9 subunit, alpha v beta 6, tenascin, and fibronectin in the proximal airways of 10 normal nonsmoking subjects and eight patients undergoing lung resection for cancer. We also performed the same analyses on sections of peripheral lung obtained from an additional seven subjects undergoing lung resection. alpha 9 was highly expressed throughout the airway epithelium (but not on alveolar epithelium) irrespective of clinical status. In contrast, alpha v beta 6 was expressed on proximal airway epithelial cells in four of eight smokers undergoing lung resection, but in none of the normal subjects and none of the distal airways examined. On bronchial epithelial cells cultured from resected airways, alpha v beta 6 was highly expressed on cells grown from patients who did not appear to express the receptor in vivo, as well as from subjects who did, suggesting that some component of the in vitro environment can induce expression. Although both tenascin and fibronectin were present below the proximal airway epithelium of both normal nonsmoking subjects and smokers, the spatial patterns of integrin and ligand expression were not congruent, because the integrins were present diffusely on the cell surface and on some cells that were not in contact with the basement membrane, whereas the ligands were present principally in the subepithelial layer. These findings are compatible with the existence of as-yet unidentified ligands for each of these integrins--for example, ligands involved in homotypic cell-cell interactions within the epithelium.

This article has been cited by other articles:

				A. N. Elayadi, K. N. Samli, L. Prudkin, Y.-H. Liu, A. Bian, X.-J. Xie, I. I. Wistuba, J. A. Roth, M. J. McGuire, and K. C. Brown A Peptide Selected by Biopanning Identifies the Integrin {alpha}v{beta}6 as a Prognostic Biomarker for Nonsmall Cell Lung Cancer Cancer Res., June 15, 2007; 67(12): 5889 - 5895. [Abstract] [Full Text] [PDF]

				T. M. McDevitt, L. W. Gonzales, R. C. Savani, and P. L. Ballard Role of endogenous TGF-beta in glucocorticoid-induced lung type II cell differentiation Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L249 - L257. [Abstract] [Full Text] [PDF]

				C. Neurohr, S. L. Nishimura, and D. Sheppard Activation of Transforming Growth Factor-beta by the Integrin {alpha}vbeta8 Delays Epithelial Wound Closure Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 252 - 259. [Abstract] [Full Text] [PDF]

				J. Roux, H. Kawakatsu, B. Gartland, M. Pespeni, D. Sheppard, M. A. Matthay, C. M. Canessa, and J.-F. Pittet Interleukin-1{beta} Decreases Expression of the Epithelial Sodium Channel {alpha}-Subunit in Alveolar Epithelial Cells via a p38 MAPK-dependent Signaling Pathway J. Biol. Chem., May 13, 2005; 280(19): 18579 - 18589. [Abstract] [Full Text] [PDF]

				M. Majumdar, T. Tarui, B. Shi, N. Akakura, W. Ruf, and Y. Takada Plasmin-induced Migration Requires Signaling through Protease-activated Receptor 1 and Integrin {alpha}9{beta}1 J. Biol. Chem., September 3, 2004; 279(36): 37528 - 37534. [Abstract] [Full Text] [PDF]

				D. SHEPPARD Functions of Pulmonary Epithelial Integrins: From Development to Disease Physiol Rev, July 1, 2003; 83(3): 673 - 686. [Abstract] [Full Text] [PDF]

				H. Duque and B. Baxt Foot-and-Mouth Disease Virus Receptors: Comparison of Bovine {alpha}V Integrin Utilization by Type A and O Viruses J. Virol., February 15, 2003; 77(4): 2500 - 2511. [Abstract] [Full Text] [PDF]

				A. V. Ljubimov, M. Saghizadeh, R. Pytela, D. Sheppard, and M. C. Kenney Increased Expression of Tenascin-C-binding Epithelial Integrins in Human Bullous Keratopathy Corneas J. Histochem. Cytochem., November 1, 2001; 49(11): 1341 - 1350. [Abstract] [Full Text] [PDF]

				D. Sheppard Integrin-Mediated Activation of Transforming Growth Factor-{beta}1 in Pulmonary Fibrosis Chest, July 1, 2001; 120(2007): 49S - 53S. [Abstract] [Full Text] [PDF]

				L. A. Miller, N. L. Barnett, D. Sheppard, and D. M. Hyde Expression of the {beta}6 Integrin Subunit Is Associated with Sites of Neutrophil Influx in Lung Epithelium J. Histochem. Cytochem., January 1, 2001; 49(1): 41 - 48. [Abstract] [Full Text]

				K. S. Spirin, A. V. Ljubimov, R. Castellon, O. Wiedoeft, M. Marano, D. Sheppard, M. C. Kenney, and D. J. Brown Analysis of Gene Expression in Human Bullous Keratopathy Corneas Containing Limiting Amounts of RNA Invest. Ophthalmol. Vis. Sci., December 1, 1999; 40(13): 3108 - 3115. [Abstract] [Full Text] [PDF]

				D. Sheppard Airway Epithelial Integrins: Why So Many? Am. J. Respir. Cell Mol. Biol., September 1, 1998; 19(3): 349 - 351. [Full Text]

				A. J. Jabbour, L. C. Altman, T. N. Wight, and D. L. Luchtel Ozone Alters the Distribution of beta 1 Integrins in Cultured Primate Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., September 1, 1998; 19(3): 357 - 365. [Abstract] [Full Text]

				S. Potter-Perigo, E. D. Kaplan, D. L. Luchtel, C. Baker, L. C. Altman, and T. N. Wight Ozone Alters the Expression of Tenascin-C in Cultured Primate Nasal Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 1998; 18(4): 471 - 478. [Abstract] [Full Text]

				A. LAITINEN, A. ALTRAJA, M. KAMPE, M. LINDEN, I. VIRTANEN, and L. A. LAITINEN Tenascin Is Increased in Airway Basement Membrane of Asthmatics and Decreased by an Inhaled Steroid Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 951 - 958. [Abstract] [Full Text] [PDF]

				L. L. Smith, H.-K. Cheung, L. E. Ling, J. Chen, D. Sheppard, R. Pytela, and C. M. Giachelli Osteopontin N-terminal Domain Contains a Cryptic Adhesive Sequence Recognized by alpha 9beta 1 Integrin J. Biol. Chem., November 8, 1996; 271(45): 28485 - 28491. [Abstract] [Full Text] [PDF]