title: A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion.
abstract: 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.
authors.affiliation: Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tasaka
authors.forename: A
authors.initials: A
authors.lastname: Ishizaka
authors.forename: T
authors.initials: T
authors.lastname: Urano
authors.forename: K
authors.initials: K
authors.lastname: Sayama
authors.forename: F
authors.initials: F
authors.lastname: Sakamaki
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Terashima
authors.forename: Y
authors.initials: Y
authors.lastname: Waki
authors.forename: K
authors.initials: K
authors.lastname: Soejima
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: S
authors.initials: S
authors.lastname: Fujishima
authors.forename: M
authors.initials: M
authors.lastname: Kanazawa
authors.forename: J W
authors.initials: JW
authors.lastname: Larrick
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D001992:Bronchoalveolar Lavage Fluid; D002352:Carrier Proteins / Q000302:isolation & purification / Q000627:therapeutic use*; D054804:Cathelicidins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000737:chemistry*; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011654:Pulmonary Edema; D011817:Rabbits
chemical_list: D000418:Albumins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D010446:Peptide Fragments