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: (l) 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, 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.
|ジャーナル||American journal of respiratory cell and molecular biology|
|出版ステータス||Published - 1996|
ASJC Scopus subject areas