| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
AJP - Lung Cellular and Molecular Physiology, Vol 262, Issue 4 386-L391, Copyright © 1992 by American Physiological Society
ARTICLES |
R. K. Scheule, R. C. Perkins, R. Hamilton and A. Holian
Department of Internal Medicine, University of Texas Medical School, Houston 77225.
Bleomycin (BLM) is a very effective antineoplastic drug for many gynecologic and urinary tract carcinomas. However, its use, e.g., cumulative dosage, often is limited by the pulmonary fibrosis that it causes. The mechanism by which BLM causes fibrosis is not understood but is proposed to involve the pulmonary macrophage, a central cell in the cytokine network of the lung. To examine the direct effects of this drug on the human alveolar macrophage, we have treated human alveolar macrophages (isolated from normal subjects by bronchoalveolar lavage) with BLM in vitro and examined resultant macrophage secretory products that have importance for inflammatory and fibrotic processes. A 24-h treatment with BLM (0.5-100 mU/ml) was found to result in 1) a concentration-dependent decrease in the ability of the macrophage to produce superoxide anion in response to phorbol 12,13-dibutyrate, 2) an increase in secreted interleukin-1 beta (IL-1 beta), and 3) a decrease in intracellular levels of adenosine 3',5'-cyclic monophosphate. Kinetic studies revealed a time-dependent appearance of BLM-induced cytokines; tumor necrosis factor-alpha could be detected as early as 4 h after stimulation, followed by IL-1 beta at 8 h. The secretion of these cytokines was found to precede the release of prostaglandin E2, which became significant only at 24 h. Taken together, the present results imply that the human alveolar macrophage does not contribute to BLM-induced oxidant injury of the lung but that it may contribute to the development of BLM-induced pulmonary fibrosis.
This article has been cited by other articles:
|
|
 |
|
  W. Huang, G. Wang, D. S. Phelps, H. Al-Mondhiry, and J. Floros Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L546 - L553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Izbicki, R. Or, T. G. Christensen, M. J. Segel, A. Fine, R. H. Goldstein, and R. Breuer Bleomycin-induced lung fibrosis in IL-4-overexpressing and knockout mice Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1110 - L1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Huang, G. Wang, D. S. Phelps, H. Al-Mondhiry, and J. Floros Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L94 - L102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sleijfer Bleomycin-Induced Pneumonitis Chest, August 1, 2001; 120(2): 617 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gurujeyalakshmi, Y. Wang, and S. N. Giri Taurine and Niacin Block Lung Injury and Fibrosis by Down-Regulating Bleomycin-Induced Activation of Transcription Nuclear Factor-kappa B in Mice J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 82 - 90. [Abstract] [Full Text]
|
|
|
|
|
|
L. Li, R. F. Hamilton Jr., and A. Holian Effect of acrolein on human alveolar macrophage NF-kappa B activity Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L550 - L557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gurujeyalakshmi, M. A. Hollinger, and S. N. Giri Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L311 - L318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Ortiz, K. Moroz, J.-Y. Liu, G. W. Hoyle, T. Hammond, R. F. Hamilton, A. Holian, W. Banks, A. R. Brody, and M. Friedman Alveolar macrophage apoptosis and TNF-alpha , but not p53, expression correlate with murine response to bleomycin Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1208 - L1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhao, S. L. Young, and J. C. McIntosh Induction of tenascin in rat lungs undergoing bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, June 1, 1998; 274(6): L1049 - L1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Hamilton Jr., L. Li, W. L. Eschenbacher, L. Szweda, and A. Holian Potential involvement of 4-hydroxynonenal in the response of human lung cells to ozone Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L8 - L16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Q. SHEN, C.-X. DUAN, Z.-Y. LI, and Y. SUZUKI Effects of Proteinosis Surfactant Proteins on the Viability of Rat Alveolar Macrophages Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1679 - 1687. [Abstract] [Full Text]
|
|
|
|
|
|
J. Chen, V. Ziboh, and S. N. Giri Up-regulation of Platelet-activating Factor Receptors in Lung and Alveolar Macrophages in the Bleomycin-Hamster Model of Pulmonary Fibrosis J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1219 - 1227. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. A. Dubaybo, G. Bayasi, and G. J. Rubeiz CHANGES IN TUMOR NECROSIS FACTOR IN POSTPNEUMONECTOMY LUNG GROWTH J. Thorac. Cardiovasc. Surg., August 1, 1995; 110(2): 396 - 404. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
