A DERIVATIVE OF CATIONIC ANTIMICROBIAL PROTEIN ATTENUATES LUNG INJURYBY SUPPRESSING CELL-ADHESION

Cationic antimicrobial protein of 18 kD (CAP18) was identified and pur ified 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. Gu inea pigs were divided into six groups: (1) saline control (n = 8), (2 ) CDF-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5) LPS+CDP (10m) (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 we t-to-dry weight ratio, [I-125]albumin leakage in lung tissue and bronc hoalveolar lavage (BAL) fluid, differential cell count in BAL fluid, a nd histopathologic features were examined 4 h after intravenous admini stration 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 attenuat ion of lung injury. The accumulation of peripheral white blood cells i nto pulmonary vasculature was attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups. We examined the effect of CDP on the expres sion of adhesion molecules using human umbilical vein endothelial cell s, the result of which showed that CDP suppressed the LPS-induced expr ession of adhesion molecules in a dose-dependent manner. We conclude t hat CDP attenuates inflammatory cell migration into alveoli resulting in the attenuation of lung injury.