Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Mice were exposed to LPS (0.5 mg kg(-1): intranasally) to induce acute lung injury. 30 minutes before and 3 hours after LPS exposure mice were subjected to vehicle or rhAPC inhalation (25 or 100 microg per mouse in each nebulization). In order to establish whether rhAPC inhalation affects neutrophil recruitment, neutrophil migration was determined in vitro using a trans-well migration assay. KEY RESULTS:
rhAPC inhalation dose-dependently decreased LPS-induced coagulation and inflammation markers in bronchoalveolar lavage fluid (BALF), reduced protein leakage into the alveolar space and improved lung function. In contrast, rhAPC did not prevent LPS-induced neutrophil recruitment into the alveolar space. Neutrophil migration in vitro towards FCS or interleukin (IL)-8 was significantly inhibited by pretreatment with rhAPC (0.01-10 microg ml(-1)], whereas rhAPC (10 microg ml(-1)) added to the chemoattractant (modelling for topical rhAPC administration) did not affect neutrophil migration towards FCS or IL-8. CONCLUSIONS AND IMPLICATIONS:
|
Authors | S H Slofstra, A P Groot, N A Maris, P H Reitsma, H Ten Cate, C A Spek |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 149
Issue 6
Pg. 740-6
(Nov 2006)
ISSN: 0007-1188 [Print] England |
PMID | 17016502
(Publication Type: Journal Article)
|
Chemical References |
- Lipopolysaccharides
- Protein C
|
Topics |
- Administration, Inhalation
- Animals
- Bronchoalveolar Lavage Fluid
- Enzyme-Linked Immunosorbent Assay
- Female
- Lipopolysaccharides
(pharmacology)
- Mice
- Mice, Inbred C57BL
- Neutrophils
(cytology, drug effects)
- Pneumonia
(prevention & control)
- Protein C
(administration & dosage, pharmacology)
- Respiratory Function Tests
|