P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine.
BACKGROUND
A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats.


METHODS
N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity.


RESULTS
Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases.


CONCLUSIONS
Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.
Serrano-Mollar
A
A
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-IDIBAPS), CSIC, Barcelona, Spain. amsbam@iibb.csic.es
Closa
D
D
Cortijo
J
J
Morcillo
E J
EJ
Prats
N
N
Gironella
M
M
Panés
J
J
Roselló-Catafau
J
J
Bulbena
O
O
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
D000903:Antibiotics, Antineoplastic; D019007:P-Selectin; D001761:Bleomycin; D009195:Peroxidase; D006909:Hydroxyproline; D000111:Acetylcysteine