Antileukinate, a Hexapeptide Inhibitor of CXC-Chemokine
Receptor, Suppresses Bleomycin-induced Acute Lung Injury in Mice.
Hayashi S, Yatsunami J, Fukuno Y, Kawashima M, Miller EJ.
Department of Internal Medicine, Saga Medical School, Saga, Japan, hayashs@post.saga-med.ac.jp
A hexapeptide, Ac-RRWWCR-NH(2) (Antileukinate), has been reported to be a potent
inhibitor of CXC-chemokine receptor. However, the in vivo anti-inflammatory
activity of this agent has not been tested except in a rabbit skin edema model.
This study was undertaken to investigate the effect of subcutaneously
administered Antileukinate on experimental bleomycin-induced acute lung injury
in mice, in which CXC-chemokines have been reported to be involved. Lung injury
was assessed on the basis of histopathology, the number of total cells, the
percentage of neutrophils, and protein concentration in the bronchoalveolar
lavage (BAL) fluid, and the wet lung weight at 7 days after intratracheal
instillation of bleomycin. Histopathological studies revealed that treatment
with Antileukinate markedly suppressed inflammatory cell infiltration and
interstitial lung edema. The neutrophil counts in the BAL fluid were
significantly decreased in the Antileukinate-treated group. The suppression of
pulmonary edema was further confirmed by the reduction of wet lung weight and
total protein concentration in the BAL fluid. These findings suggest that
Antileukinate is able to inhibit acute lung injury by suppressing neutrophil
mobilization induced by CXC-chemokines.
