| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; and
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
Increased numbers of T lymphocytes are observed in the lungs of patients with chronic obstructive pulmonary disease, but their role in the disease process is not known. We investigated the role of CD8+ T cells in inflammatory cell recruitment and lung destruction in a cigarette smoke-induced murine model of emphysema. In contrast to wild-type C57BL/6J mice that displayed macrophage, lymphocyte, and neutrophil recruitment to the lung followed by emphysema in response to cigarette smoke, CD8+ T cell-deficient (CD8–/–) mice had a blunted inflammatory response and did not develop emphysema when exposed to long-term cigarette smoke. Further studies supported a pathogenetic pathway whereby the CD8+ T cell product, IFN-
-inducible protein-10, induces production of macrophage elastase (matrix metalloproteinase 12) that degrades elastin, both causing lung destruction directly and generating elastin fragments that serve as monocyte chemokines augmenting macrophage-mediated lung destruction. These studies demonstrate a requirement for CD8+ T cells for the development of cigarette smoke-induced emphysema and they provide a unifying pathway whereby CD8+ T cells are a central regulator of the inflammatory network in chronic obstructive pulmonary disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported, in part, by grants from the National Heart, Lung, and Blood Institute (to S.D.S.).
2 Address correspondence and reprint requests to Dr. Steven D. Shapiro, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, NW 628 Montefiore, 3459 Fifth Avenue, Pittsburgh, PA 15213. E-mail address: ShapiroS{at}dom.pitt.edu
3 Abbreviations used in this paper: COPD, chronic obstructive pulmonary disease; MMP-12, matrix metalloproteinase 12; EF, elastin fragment; IP-10, IFN--inducible protein 10; WT, wild type; Lm, mean linear intercept; BAL, bronchoalveolar lavage; hpf, high-powered field.
This article has been cited by other articles:
|
|
 |
|
  P. J. Christensen, A. M. Preston, T. Ling, M. Du, W. B. Fields, J. L. Curtis, and J. M. Beck Pneumocystis murina Infection and Cigarette Smoke Exposure Interact To Cause Increased Organism Burden, Development of Airspace Enlargement, and Pulmonary Inflammation in Mice Infect. Immun., August 1, 2008; 76(8): 3481 - 3490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Tuder, J. H. Yun, and B. B. Graham Cigarette Smoke Triggers Code Red: p21CIP1/WAF1/SDI1 Switches on Danger Responses in the Lung Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 1 - 6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Wright, M. Cosio, and A. Churg Animal models of chronic obstructive pulmonary disease Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L1 - L15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Chung and I. M. Adcock Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction Eur. Respir. J., June 1, 2008; 31(6): 1334 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Koff, M. X. G. Shao, I. F. Ueki, and J. A. Nadel Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1068 - L1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yao, I. Edirisinghe, S. Rajendrasozhan, S.-R. Yang, S. Caito, D. Adenuga, and I. Rahman Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1174 - L1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Churg, M. Cosio, and J. L. Wright Mechanisms of cigarette smoke-induced COPD: insights from animal models Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L612 - L631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Baraldo and M. Saetta To reg or not to reg: that is the question in COPD Eur. Respir. J., March 1, 2008; 31(3): 486 - 488. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
