Protective effects of selectin chimeras in neutrophil-mediated lung injury

Autor: M S Mulligan, S R Watson, C Fennie, P A Ward
Rok vydání: 1993
Předmět:
Zdroj: The Journal of Immunology. 151:6410-6417
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.151.11.6410
Popis: Recombinant selectin chimeric molecules featuring the joining of the extracellular domains of L-, P-, and E-selectin to the CH2 and CH3 domains of human IgG1 have been evaluated for their ability to protect against neutrophil-dependent lung injury in rats after systemic activation of C caused by vascular infusion of cobra venom factor (CVF) or lung injury that follows intrapulmonary deposition of IgG immune complexes. Previous studies using anti-selectin antibodies have suggested that the former model is P-selectin dependent, whereas the latter is E-selectin dependent. Requirements for L-selectin have not been identified because of lack of reagents. For the current studies employing the CVF model of lung injury, infusion of P-selectin-Ig chimera reduced injury (as assessed by changes in permeability and hemorrhage) in a dose-dependent manner, with parallel reductions in lung myeloperoxidase (MPO) content. Similar results were obtained with the L-selectin-Ig chimera, whereas the E-selectin-Ig chimera was not protective and failed to alter MPO content. In contrast, in the IgG immune complex model of lung injury, the L- and E-selectin-Ig chimeras both showed dose-related protective effects and reductions in MPO content, whereas the P-selectin-Ig chimera failed to protect against injury and did not alter MPO content in this model of lung injury. In all cases of blocking of injury, this was incomplete, suggesting multi-selectin engagement or inadequate amounts of selectin-Ig chimeras employed. These data indicate that neutrophil recruitment and attendant lung injury in the CVF model are L- and P-selectin dependent and E-selectin-independent, whereas in the IgG immune complex model, neutrophil recruitment and lung injury are L- and E-selectin-dependent but independent of P-selectin. Thus, differing selectin requirements for acute inflammatory lung injury have been identified.
Databáze: OpenAIRE
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