Am. J. Respir. Cell Mol. Biol., Vol 15, No. 6, 12 1996, 738-744.
A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion
S Tasaka, A Ishizaka, T Urano, K Sayama, F Sakamaki, H Nakamura, T Terashima, Y Waki, K Soejima, M Nakamura, H Matsubara, S Fujishima, M Kanazawa and JW Larrick
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Cationic antimicrobial protein of 18 kD (CAP18) was identified and purified
from rabbit granulocytes and shown to inhibit various activities of
lipopolysaccharide (LPS). We investigated the effect of a 32-amino-acid
C-terminal fragment of CAP18 (CAP18-derived peptide, CDP) on the
pathogenesis of acute lung injury caused by intravenous endotoxin. Guinea
pigs were divided into six groups: (I) saline control (n = 8), (2)
CDP-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5)
LPS+CDP10m (n = 8), and (6) LPS+CDP60m (n = 8). A CDP dose of 0.2 mg/kg was
injected at various time points after LPS injection. Lung wet-to-dry weight
ratio, [125I]albumin leakage in lung tissue and bronchoalveolar lavage
(BAL) fluid, differential cell count in BAL fluid, and histopathologic
features were examined 4 h after intravenous administration of 0.02 mg/kg
of LPS. The LPS+CDP0m and the LPS+CDP10m groups showed significantly
attenuated lung injury compared to that seen in the LPS-alone group,
however the LPS+CDP60m group revealed no attenuation of lung injury. The
accumulation of peripheral white blood cells into pulmonary vasculature was
attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups. We
examined the effect of CDP on the expression of adhesion molecules using
human umbilical vein endothelial cells, the result of which showed that CDP
suppressed the LPS-induced expression of adhesion molecules in a
dose-dependent manner. We conclude that CDP attenuates inflammatory cell
migration into alveoli resulting in the attenuation of lung injury.
