Sepsis-induced acute lung injury is attenuated by selectin blockade following the onset of sepsis
P. C. Ridings, G. L. Bloomfield, S. Holloway, A. C. Windsor, M. A. Jutila, A. A. Fowler 3rd and H. J. Sugerman
Department of Surgery, Medical College of Virginia, USA.
OBJECTIVE: To determine the effect of infusion with a dual-binding antibody
to E- and L-selectin, EL-246, in a postonset model of sepsis. DESIGN:
Nonrandomized controlled study. STUDY SUBJECTS: Young Yorkshire swine.
INTERVENTIONS: Three groups were studied. Controls (n = 8) received saline
solution only. Untreated animals with sepsis (n = 8) received a 1-hour
intravenous infusion of live Pseudomonas aeruginosa. Animals treated with
EL-246 (n = 6) received the same bacterial infusion and a 2-mg/kg bolus of
EL-246 at 30 minutes. OUTCOME MEASURES: Systemic and pulmonary
hemodynamics, arterial blood gas determination, bronchoalveolar lavage
protein and neutrophil content, neutrophil integrin and selectin
expression, neutrophil oxidant burst, and organ myeloperoxidase content.
RESULTS: Treatment with EL-246 significantly reduced lung injury, as
indicated by improved bronchoalveolar lavage protein and neutrophil
content, resulting in a significant improvement in arterial oxygenation.
This reduction in lung injury was produced by a reduction in lung
myeloperoxidase content. Treatment with EL-246 failed to prevent the
development of pulmonary hypertension and systemic hypotension. Neutrophils
from animals with sepsis exhibited significant activation and upregulation
of CD18, shedding of L-selectin, and production of increased levels of
oxidants compared with controls. CONCLUSION: Treatment of animals with
EL-246 soon the onset of sepsis produced significant protection against
acute lung injury but failed to attenuate hemodynamic derangements
associated with sepsis.
