help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on December 18, 2003, doi:10.1164/rccm.200302-224OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200302-224OCv1
169/6/687    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Holtzclaw, J. D.
Right arrow Articles by Hsu, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Holtzclaw, J. D.
Right arrow Articles by Hsu, L. L.
American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 687-695, (2004)
© 2004 American Thoracic Society

Original Article

Enhanced Pulmonary and Systemic Response to Endotoxin in Transgenic Sickle Mice

J. David Holtzclaw, Daniel Jack, Samuel M. Aguayo, James R. Eckman, Jesse Roman and Lewis L. Hsu

Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia

Correspondence and requests for reprints should be addressed to Lewis L. Hsu, M.D., Ph.D., Pediatric Hematology, St. Christopher's Hospital for Children, Drexel University College of Medicine, Erie Ave. at Front St., Philadelphia, PA 19134. E-mail: Lewis.Hsu{at}tenethealth.com

Some suggest that sickle cell disease (SCD) is associated with a "proinflammatory state" that predisposes patients to acute chest syndrome in the setting of triggering factors. Conflicting data emerged when inflammation markers in SCD were compared with healthy individuals. Therefore, we examined transgenic sickle and control mice at baseline and with endotoxin (LPS) intraperitoneal injection to determine whether a proinflammatory state truly exists. At baseline, sickle mice had elevated levels of circulating leukocytes and soluble vascular cell adhesion molecule 1 (sVCAM-1). No other differences were observed at baseline or in response to saline. However, LPS challenge was associated with significant increases in mortality (p < 0.05), airway tone (p < 0.03), serum and bronchoalveolar lavage levels of cytokines tumor necrosis factor-{alpha} (p < 0.03), interleukin-1ß (p < 0.02), and sVCAM-1 (p < 0.01) in sickle mice compared with control subjects. Furthermore, 4 hours after LPS, microarray analysis identified 413 genes differentially expressed in the sickle mice (n = 5) compared with only 7 in the control subjects (n = 5). No difference in lung parenchyma was observed by light microscopy. This enhanced response to LPS suggests that the sickle red blood cell confers a subclinical "proinflammatory state." This enhanced response to inflammatory insult, particularly by adhesion molecules such as sVCAM-1, could play a role in the increased susceptibility to pulmonary dysfunction that has been observed clinically in SCD.

Key Words: inflammation • cytokines • adhesion molecules • plethysmography • cDNA microarray




This article has been cited by other articles:


Home page
 NEJMHome page
M. T. Gladwin and E. Vichinsky
Pulmonary Complications of Sickle Cell Disease
N. Engl. J. Med., November 20, 2008; 359(21): 2254 - 2265.
[Full Text] [PDF]

Home page
 BloodHome page
S. D. Nandedkar, T. R. Feroah, W. Hutchins, D. Weihrauch, K. S. Konduri, J. Wang, R. C. Strunk, M. R. DeBaun, C. A. Hillery, and K. A. Pritchard
Histopathology of experimentally induced asthma in a murine model of sickle cell disease
Blood, September 15, 2008; 112(6): 2529 - 2538.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. L. Hsu, H. C. Champion, S. A. Campbell-Lee, T. J. Bivalacqua, E. A. Manci, B. A. Diwan, D. M. Schimel, A. E. Cochard, X. Wang, A. N. Schechter, et al.
Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability
Blood, April 1, 2007; 109(7): 3088 - 3098.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
Poster presentations
Thorax, December 1, 2006; 61(suppl_2): ii57 - ii133.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. D. Bradley, Y. E. Miller, F. J. Martinez, D. C. Angus, W. MacNee, and E. Abraham
Interstitial Lung Disease, Lung Cancer, Lung Transplantation, Pulmonary Vascular Disorders, and Sleep-disordered Breathing in AJRCCM in 2004
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 675 - 685.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Greenough
Sickle Cell Disease--Pulmonary Complications and a Proinflammatory State?
Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 663 - 665.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society 		  ATS Quiz on Sleep Study Tracings