Protective Effects of Selectin Chimeras in Neutrophil-Mediated Lung Injury

摘要: Recombinant selectin chimeric molecules featuring the joining of extracellular domains L-, P-, and E-selectin to CH2 CH3 human IgG1 have been evaluated for their ability protect against neutrophil-dependent lung injury in rats after systemic activation C caused by vascular infusion cobra venom factor (CVF) or that follows intrapulmonary deposition IgG immune complexes. Previous studies using anti-selectin antibodies suggested former model is P-selectin dependent, whereas latter dependent. Requirements L-selectin not identified because lack reagents. For current employing CVF injury, P-selectin-Ig chimera reduced (as assessed changes permeability hemorrhage) a dose-dependent manner, with parallel reductions myeloperoxidase (MPO) content. Similar results were obtained L-selectin-Ig chimera, E-selectin-Ig was protective failed alter MPO In contrast, complex L- chimeras both showed dose-related effects content, did content this injury. all cases blocking incomplete, suggesting multi-selectin engagement inadequate amounts selectin-Ig employed. These data indicate neutrophil recruitment attendant are dependent E-selectin-independent, model, E-selectin-dependent but independent P-selectin. Thus, differing requirements acute inflammatory identified.