| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Anaesthesia and Critical Care Medicine, St. Michael's Hospital, Toronto M5B 1W8; 2 Department of Pathology and Laboratory Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5; and 3 Division of Thoracic Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario M5G 2C4, Canada
High concentrations of
neutrophil defensins from airway and blood have been reported in
patients with inflammatory lung diseases, but their exact role is
unclear. We investigated the direct effect of defensins on the lungs of
mice. Intratracheal instillation of purified defensins (5-30
mg/kg) induced a progressive reduction in peripheral arterial
O2 saturation, increased lung permeability, and enhanced
the lung cytochrome c content. These indexes of acute lung
dysfunction were associated with an increased total cell number and a
significant neutrophil influx into the lung [5.1 ± 0.04% in
control vs. 48.6 ± 12.7% in the defensin (30 mg/kg) group,
P < 0.05]. Elastase concentrations in the
bronchoalveolar lavage (BAL) fluids increased from 38 ± 11 ng/ml
(control) to 80 ± 4 ng/ml (defensins, P < 0.05).
Five hours after defensin instillation, concentrations of tumor
necrosis factor-
and macrophage inflammatory protein-2 in
BAL fluid were significantly increased. High levels of monocyte
chemoattractant protein-1 in BAL fluid and plasma were also found after
defensin stimulation. We conclude that intratracheal instillation of
defensins causes acute lung inflammation and dysfunction, suggesting
that high concentrations of defensins in the airways may play an
important role in the pathogenesis of inflammatory lung diseases.
cytokine; inflammatory lung disease; human neutrophil peptides
This article has been cited by other articles:
|
|
 |
|
  M. Doss, M. R. White, T. Tecle, and K. L. Hartshorn Human defensins and LL-37 in mucosal immunity J. Leukoc. Biol., January 1, 2010; 87(1): 79 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Voglis, K. Quinn, E. Tullis, M. Liu, M. Henriques, C. Zubrinich, O. Penuelas, H. Chan, F. Silverman, V. Cherepanov, et al. Human Neutrophil Peptides and Phagocytic Deficiency in Bronchiectatic Lungs Am. J. Respir. Crit. Care Med., July 15, 2009; 180(2): 159 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Zemans, S. P. Colgan, and G. P. Downey Transepithelial Migration of Neutrophils: Mechanisms and Implications for Acute Lung Injury Am. J. Respir. Cell Mol. Biol., May 1, 2009; 40(5): 519 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Quinn, M. Henriques, T. Parker, A. S. Slutsky, and H. Zhang Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1817 - H1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vaschetto, J. Grinstein, L. Del Sorbo, A. A. Khine, S. Voglis, E. Tullis, A. S. Slutsky, and H. Zhang Role of human neutrophil peptides in the initial interaction between lung epithelial cells and CD4+ lymphocytes J. Leukoc. Biol., April 1, 2007; 81(4): 1022 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Khine, L. Del Sorbo, R. Vaschetto, S. Voglis, E. Tullis, A. S. Slutsky, G. P. Downey, and H. Zhang Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway Blood, April 1, 2006; 107(7): 2936 - 2942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Economopoulou, K. Bdeir, D. B. Cines, F. Fogt, Y. Bdeir, J. Lubkowski, W. Lu, K. T. Preissner, H.-P. Hammes, and T. Chavakis Inhibition of pathologic retinal neovascularization by {alpha}-defensins Blood, December 1, 2005; 106(12): 3831 - 3838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. van Wetering, G. S. Tjabringa, and P. S. Hiemstra Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells J. Leukoc. Biol., April 1, 2005; 77(4): 444 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Tjabringa, J. Aarbiou, D. K. Ninaber, J. W. Drijfhout, O. E. Sorensen, N. Borregaard, K. F. Rabe, and P. S. Hiemstra The Antimicrobial Peptide LL-37 Activates Innate Immunity at the Airway Epithelial Surface by Transactivation of the Epidermal Growth Factor Receptor J. Immunol., December 15, 2003; 171(12): 6690 - 6696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Klut, B. A. Whalen, and J. C. Hogg Dynamic Changes in Neutrophil Defensins during Endotoxemia Infect. Immun., December 1, 2001; 69(12): 7793 - 7799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Porro, J.-H. Lee, J. de Azavedo, I. Crandall, T. Whitehead, E. Tullis, T. Ganz, M. Liu, A. S. Slutsky, and H. Zhang Direct and indirect bacterial killing functions of neutrophil defensins in lung explants Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1240 - L1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Lopez-Boado, C. L. Wilson, and W. C. Parks Regulation of Matrilysin Expression in Airway Epithelial Cells by Pseudomonas aeruginosa Flagellin J. Biol. Chem., October 26, 2001; 276(44): 41417 - 41423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Olson, K. Singbartl, and K. Ley L-selectin is required for fMLP- but not C5a-induced margination of neutrophils in pulmonary circulation Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1245 - R1252. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
