Endothelial selectin blockade attenuates lung permeability of experimental acid aspiration.
BACKGROUND
A central role for the polymorphonuclear leukocyte (PMN) in experimental acid aspiration has been demonstrated by the observation that PMN depletion reduced pulmonary vascular permeability. This study investigates the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating acid aspiration lung injury.


METHODS
Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of (125)I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed.


RESULTS
PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 1 mg/kg rPSGL-Ig before acid aspiration. PMN count of 19 +/- 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 +/- 72. The respective PI in mice treated with rPSGL-Ig (1/2) hour and 1 hour after acid aspiration was 45% and 39% reduced compared with the untreated group.


CONCLUSIONS
Endothelial selectin blockade is as effective as PMN depletion in moderating acid aspiration induced lung permeability. Delayed antiselectin therapy can decrease lung injury.
Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
C
C
Kyriakides
W
W
Austen
Y
Y
Wang
J
J
Favuzza
F D
FD
Moore
H B
HB
Hechtman
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D019040:E-Selectin / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity*; D001239:Inhalation; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea
D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011994:Recombinant Proteins; D006851:Hydrochloric Acid