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

Abstract

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.

• Authors: P C Ridings, G L Bloomfield, S Holloway, A C Windsor, M A Jutila, A A Fowler 3rd, H J Sugerman
• Journal: Archives of surgery (Chicago, Ill. : 1960) (Arch Surg) Vol. 130 Issue 11 Pg. 1199-208 (Nov 1995) ISSN: 0004-0010 [Print] United States
• PMID: 7487463 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies
• Selectins

Topics

• Animals
• Antibodies (therapeutic use)
• Hemodynamics
• Lung Diseases (metabolism, microbiology, physiopathology, prevention & control)
• Neutrophils (physiology)
• Selectins (biosynthesis, immunology)
• Sepsis (complications, metabolism, physiopathology)
• Swine