| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the University of Minnesota, Minneapolis, MN.
Correspondence to: Imad Y. Haddad, MD, Division of Pediatric Pulmonary and Critical Care, University of Minnesota Medical School, 420 Delaware St SE, Box 742, Minneapolis, MN 55455
A major complication of human bone marrow transplantation (BMT) is the development of noninfectious diffuse lung damage referred to as idiopathic pneumonia syndrome (IPS). We hypothesized that T cell-mediated immune responses are critical for the development of IPS. Alloresponsive donor T cells activate host alveolar macrophages (AMs) to release tissue-damaging reactive oxygen and nitrogen species such as nitric oxide (NO) and peroxynitrite. In a model of BMT in irradiated B10.BR mice, injection of C57BL/6 T cells at the time of BMT resulted in histologic evidence of lung injury associated with the following: (1) fivefold increase in lactate dehydrogenase and total protein detected in the BAL fluid measured at day 7; (2) increased systemic levels of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha; and (3) lung infiltration with T cells co-localized with host macrophages, with an increase in major histocompatibility complex class II antigens expression as detected by monoclonal antibodies. Irradiated and transplanted mice not injected with T cells did not develop lung dysfunction, and their lactate dehydrogenase and protein levels in the BAL were at baseline values. AMs obtained from the BAL 7 days following BMT were cultured on IgG-plated wells (2 x 105 per well) for 48 h and the stable NO product, nitrite (Greiss reaction), in the supernant was measured. In contrast to cells obtained from irradiated animals that did not produce NO, AMs from mice injected with T cells expressed the inducible form of NO synthase protein, and spontaneously generated large amounts of NO (nitrite 20 µM; n = 6). Mice preconditioned with cyclophosphamide (120 mg/kg/d on days -3 and -2) and injected with T cells developed significantly worst lung dysfunction, and their AMs spontaneously produced maximal amounts of NO (nitrite 40.8 µM; n = 6). The inducible form of NO synthase messenger RNA was detected in lung tissue of mice injected with T cells. We conclude that T-cell responses are critical for the development of IPS. Activation of AM correlates with development of lung dysfunction and induction of NO generation.
This article has been cited by other articles:
|
|
 |
|
  S. Inoue, H. Nakamura, K. Otake, H. Saito, K. Terashita, J. Sato, H. Takeda, and H. Tomoike Impaired Pulmonary Inflammatory Responses Are a Prominent Feature of Streptococcal Pneumonia in Mice with Experimental Emphysema Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 764 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Daddi, T. Suda, F. D'Ovidio, S. A. Kanaan, T. Tagawa, K. Grapperhaus, B. D. Kozower, J. H. Ritter, N. S Yew, T. Mohanakumar, et al. Recipient intramuscular cotransfection of naked plasmid transforming growth factor {beta}1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury J. Thorac. Cardiovasc. Surg., August 1, 2002; 124(2): 259 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tasaka, S. E. Richer, J. P. Mizgerd, and C. M. Doerschuk Very Late Antigen-4 in CD18-Independent Neutrophil Emigration during Acute Bacterial Pneumonia in Mice Am. J. Respir. Crit. Care Med., July 1, 2002; 166(1): 53 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-p. Gao, T. J. Standiford, A. Rahman, M. Newstead, S. M. Holland, M. C. Dinauer, Q.-h. Liu, and A. B. Malik Role of NADPH Oxidase in the Mechanism of Lung Neutrophil Sequestration and Microvessel Injury Induced by Gram-Negative Sepsis: Studies in p47phox-/- and gp91phox-/- Mice J. Immunol., April 15, 2002; 168(8): 3974 - 3982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Saito, J. Lai, R. Rogers, and C. M. Doerschuk Mechanical properties of rat bone marrow and circulating neutrophils and their responses to inflammatory mediators Blood, March 15, 2002; 99(6): 2207 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-p. Gao, N. Xu, M. Sekosan, D. Mehta, S. Y. Ma, A. Rahman, and A. B. Malik Differential Role of CD18 Integrins in Mediating Lung Neutrophil Sequestration and Increased Microvascular Permeability Induced by Escherichia coli in Mice J. Immunol., September 1, 2001; 167(5): 2895 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Alcamo, J. P. Mizgerd, B. H. Horwitz, R. Bronson, A. A. Beg, M. Scott, C. M. Doerschuk, R. O. Hynes, and D. Baltimore Targeted Mutation of TNF Receptor I Rescues the RelA-Deficient Mouse and Reveals a Critical Role for NF-{kappa}B in Leukocyte Recruitment J. Immunol., August 1, 2001; 167(3): 1592 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Lush, G. Cepinskas, W. J. Sibbald, and P. R. Kvietys Endothelial E- and P-selectin expression in iNOS- deficient mice exposed to polymicrobial sepsis Am J Physiol Gastrointest Liver Physiol, February 1, 2001; 280(2): G291 - G297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Cooke, G. R. Hill, A. Gerbitz, L. Kobzik, T. R. Martin, J. M. Crawford, J. P. Brewer, and J. L. M. Ferrara Hyporesponsiveness of Donor Cells to Lipopolysaccharide Stimulation Reduces the Severity of Experimental Idiopathic Pneumonia Syndrome: Potential Role for a Gut-Lung Axis of Inflammation J. Immunol., December 1, 2000; 165(11): 6612 - 6619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Doerschuk, S. Tasaka, and Q. Wang CD11/CD18-Dependent and -Independent Neutrophil Emigration in the Lungs . How Do Neutrophils Know Which Route to Take? Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 133 - 136. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
