Sepsis-induced acute lung injury is attenuated by selectin blockade following the onset of sepsis.
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.


METHODS
Nonrandomized controlled study.


METHODS
Young Yorkshire swine.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D006439:Hemodynamics; D008171:Lung Diseases / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D009504:Neutrophils / Q000502:physiology; D019087:Selectins / Q000096:biosynthesis* / Q000276:immunology; D018805:Sepsis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013552:Swine
D000906:Antibodies; D019087:Selectins