| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: xgao{at}uic.edu.
Since lung vascular injury is characteristic of sepsis-induced lung injury, we examined the relationship between the influx of neutrophils (PMN) and the development of lung vascular injury in response to E. coli pneumonia. We assessed pulmonary vascular PMN sequestration by measuring lung tissue myeloperoxidase (MPO) and transvascular PMN migration by determining PMN counts in lung interstitium and bronchoalveolar lavage fluid (BALF) in mice challenged intratracheally (i.t.) with E. coli. Lung vascular injury was quantified by determining the microvessel filtration coefficient (Kf,c), a measure of vascular permeability. We also addressed the role of CD18 integrin in the mechanisms of PMN migration and lung vascular injury by inducing the expression of Neutrophil Inhibitory Factor (NIF), a specific CD11/CD18 antagonist that blocks PMN adhesion to endothelial cells. In control animals, we observed time-dependent 6-fold increase in PMN sequestration at the 6 hr time points after challenge and a 5-fold increase in airway PMN migration such that 90% of BALF cells were PMN. The lung interstitial PMN uptake increased 20-fold at 6 hr after E. coli challenge. Interestingly, Kf,c increased minimally during this period of PMN extravasation. Blockade of CD11/CD18 with NIF reduced the lung tissue PMN sequestration consistent with the role of CD18 in mediating PMN adhesion, but failed to significantly alter the PMN migration response. Moreover, CD11/CD18 blockade by NIF did not significantly affect Kf,c. Analysis of BALF leukocytes from i.t. E. coli challenged mice demonstrated a diminished respiratory oxidative burst compared to BALF leukocytes from bacteremic mice, suggesting a basis for the attenuated lung vascular injury. The massive CD11/CD18-independent airway PMN influx elicited by E. coli pneumonia is indicative of an efficient host-defense response since migration occurred in the absence of significant lung vascular injury and tissue edema.
This article has been cited by other articles:
|
|
 |
|
  V. Brovkovych, X.-P. Gao, E. Ong, S. Brovkovych, M.-L. Brennan, X. Su, S. L. Hazen, A. B. Malik, and R. A. Skidgel Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L96 - L103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Broman, P. Kouklis, X. Gao, R. Ramchandran, R. F. Neamu, R. D. Minshall, and A. B. Malik Cdc42 Regulates Adherens Junction Stability and Endothelial Permeability by Inducing {alpha}-Catenin Interaction With the Vascular Endothelial Cadherin Complex Circ. Res., January 6, 2006; 98(1): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeyaseelan, R. Manzer, S. K. Young, M. Yamamoto, S. Akira, R. J. Mason, and G. S. Worthen Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses against Escherichia coli Lipopolysaccharide and Viable Escherichia coli J. Immunol., December 1, 2005; 175(11): 7484 - 7495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-P. Gao, Q. Liu, M. Broman, D. Predescu, R. S. Frey, and A. B. Malik Inactivation of CD11b in a mouse transgenic model protects against sepsis-induced lung PMN infiltration and vascular injury Physiol Genomics, April 14, 2005; 21(2): 230 - 242. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
