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Survival in lung reperfusion injury is improved by an antibody that binds and inhibits L- and E-selectin.

Abstract
The selectins are a three-member family of leukocyte, platelet, and endothelial cell adhesion proteins that mediate leukocyte traffic into normal and inflamed tissues. P-selectin is expressed by endothelial cells and platelets, E-selectin by endothelial cells, and L-selectin by circulating leukocytes. To determine if selectin-mediated leukocyte adhesion influences the development of lung reperfusion injury, we studied hemodynamics and respiratory and inert gas exchange in sheep subjected to 3-hour in situ left lung ischemia followed by 6-hour left lung reperfusion with the right lung excluded. Ten minutes before reperfusion, eight animals received EL-246 (1 mg/kg intravenously), a novel antihuman selectin antibody that recognizes and blocks both L- and E-selectin and cross-reacts in sheep. Eight control animals with ischemia received no treatment, whereas three received an isotype-matched antihuman L-selectin antibody that does not cross-react in sheep (DREG-56, 1 mg/kg intravenously). Eight sham control sheep underwent an identical operative procedure but were never subjected to ischemia. Volume-cycled, pressure-limited (20 cm H2O) mechanical ventilation was consistent in all animals throughout the experiment. Six-hour survival in EL-246 recipients (100%) was significantly higher than in either ischemic control sheep (37.5%) or DREG-56 recipients (33.3%), but gravimetric lung water was equivalent in EL-246 recipients (5.9 +/- 1.7 ml/kg), ischemic control sheep (8.3 +/- 3.0 ml/kg), and DREG-56 recipients (9.1 +/- 2.6 ml/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsJ B Steinberg, H Z Mao, S D Niles, M A Jutila, D P Kapelanski
JournalThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) 1994 Mar-Apr Vol. 13 Issue 2 Pg. 306-18 ISSN: 1053-2498 [Print] United States
PMID7518251 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • E-Selectin
  • L-Selectin
  • Carbon Dioxide
  • Oxygen
Topics
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Carbon Dioxide (blood)
  • Cell Adhesion Molecules (immunology)
  • Cross Reactions (immunology)
  • E-Selectin
  • Female
  • Infusions, Intravenous
  • L-Selectin
  • Lung (blood supply)
  • Mice
  • Oxygen (blood)
  • Reperfusion Injury (immunology, therapy)
  • Sheep
  • Vascular Resistance (drug effects)

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