Περίληψη:
The serine protease activated protein C (APC) possesses prominent
anticoagulant and anti-inflammatory actions. In this study, we
investigated the effect of inhaled recombinant human (rh) APC in a
murine lung injury model. Animals inhaled 10 mg of Pseudomonas
lipopolysaccharide (LPS) in 3 mL normal saline (NS); 3 0 min prior to
LPS, mice were pretreated with inhaled rhAPC (4 mg/3 mL NS; APC + LPS
group) or NS (LPS group), A control animal group inhaled vehicle (NS)
twice. 24 h later, total cells and cell-types, protein content, and the
cytokines tumor necrosis factor-a, interleukin (IL)-6, macrophage
inflammatory protein-la, and mouse keratinocyte-derived chemokine (a
homolog of human IL-8) were estimated in bronchoalveolar lavage fluid
(BALF). Lung pathology given as total histology score (THS), wet/dry
lung weight ratios, and lung vascular cell adhesion molecule (VCAM)-1
expression were additionally assessed. rhAPC inhalation attenuated the
aerosolized LPS-induced increases of. total cells, nentrophils and
macrophages in BALF, lung tissue VCAM-1 protein levels, and THS. Total
protein levels and cytokines in BALF, and wet/dry weight ratios were
increased in the LPS group, but rhAPC pretreatment did not significantly
alter the LPS-induced responses. In conclusion, in this murine septic
model of lung injury, inhaled rhAPC appears to attenuate lung
inflammation, without reversing the observed increases in lung
permeability and BALF cytokines. This effect may be associated with
leukocyte trafficking modifications, related, at least in part, to
VCAM-1 reduction. (c) 2006 Elsevier Inc. All rights reserved.
Συγγραφείς:
Kotanidou, Anastasia
Loutrari, Heleni
Papadomichelakis,
Evangelos
Glynos, Constantinos
Magkou, Christina and
Armaganidis, Apostolos
Papapetropoulos, Andreas
Roussos, Charis
and Orfanos, Stylianos E.
