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Am J Physiol Lung Cell Mol Physiol 281: L1494-L1499, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 6, L1494-L1499, December 2001

Sialyl Lewisx hybridized complement receptor type 1 moderates acid aspiration injury

Constantinos Kyriakides1, Yong Wang1, William G. Austen Jr.1, Joanne Favuzza1, Lester Kobzik2, Francis D. Moore Jr.1, and Herbert B. Hechtman1

Departments of 1 Surgery and 2 Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

The potentially enhanced anti-inflammatory effects of the sialyl Lewisx (sLex)-decorated version of soluble complement receptor type 1 (sCR1) in moderating acid aspiration injury are examined. HCl was instilled in tracheostomy tubes placed in mice, and extravasation of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid was used to calculate the vascular permeability index (PI). Neutrophil counts in BAL fluid and immunohistochemistry were performed. PI was moderated by 82% after treatment with sCR1sLex compared with 54% in sCR1-untreated mice (P < 0.05). Respective reductions in PI in mice treated 0.5 and 1 h after acid aspiration with sCR1sLex of 70 and 57% were greater than the decreases in PI of 45 and 38% observed in respective sCR1-treated groups (P < 0.05). BAL fluid neutrophil counts in sCR1sLex-treated mice were significantly less than those in sCR1-treated animals, which were similar to those in untreated mice. Immunohistochemistry stained for sCR1 only on the pulmonary vascular endothelium of sCR1sLex- but not sCR1-treated mice. In conclusion, sCR1sLex moderates permeability by antagonizing complement activation and neutrophil adhesion. Delayed complement and neutrophil antagonism significantly reduces injury.

pneumonia; murine; inflammation; complement activation; selectins


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