| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1662
We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h × 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h × 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.
adhesion molecule; neutrophil; sepsis; pneumonia; acute lung injury
This article has been cited by other articles:
|
|
 |
|
  A. L. Humlicek, L. Pang, and D. C. Look Modulation of airway inflammation and bacterial clearance by epithelial cell ICAM-1 Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L598 - L607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hamaguchi, Y. Nishizawa, M. Yasui, M. Hasegawa, Y. Kaburagi, K. Komura, T. Nagaoka, E. Saito, Y. Shimada, K. Takehara, et al. Intercellular Adhesion Molecule-1 and L-Selectin Regulate Bleomycin-Induced Lung Fibrosis Am. J. Pathol., November 1, 2002; 161(5): 1607 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Moreland, R. M. Fuhrman, J. A. Pruessner, and D. A. Schwartz CD11b and Intercellular Adhesion Molecule-1 Are Involved in Pulmonary Neutrophil Recruitment in Lipopolysaccharide-Induced Airway Disease Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 474 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. WELTY-WOLF, M. S. CARRAWAY, Y.-C. T. HUANG, S. G. SIMONSON, S. P. KANTROW, T. K. KISHIMOTO, and C. A. PIANTADOSI Antibody to Intercellular Adhesion Molecule 1 (CD54) Decreases Survival and Not Lung Injury in Baboons with Sepsis Am. J. Respir. Crit. Care Med., March 1, 2001; 163(3): 665 - 673. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
