A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion.
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.
Tasaka
S
S
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ishizaka
A
A
Urano
T
T
Sayama
K
K
Sakamaki
F
F
Nakamura
H
H
Terashima
T
T
Waki
Y
Y
Soejima
K
K
Nakamura
M
M
Matsubara
H
H
Fujishima
S
S
Kanazawa
M
M
Larrick
J W
JW
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
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