Using our recently described model of
acute lung injury in rats after systemic activation of
complement by
cobra venom factor (CVF), we demonstrated that pretreatment of animals with human milk
apolactoferrin (in its native or derivatized form), but not
iron-saturated
lactoferrin, provides significant protection against
complement- and neutrophil-mediated
lung injury. The synthetic
iron chelator deferoxamine mesylate also affords protection from
lung injury. The protective effects of
apolactoferrin are not related to a blocking of CVF-induced complement activation. We also demonstrated that infusion of ionic
iron, especially Fe3+, greatly potentiates lung
vascular injury after systemic complement activation. Finally, protection from
lung injury occurs in animals pretreated with the potent scavenger of
hydroxyl radicals (
OH.),
dimethyl sulfoxide. Based on transmission electron microscopy, CVF-treated rats show leukoaggregates and endothelial cell destruction in interstitial pulmonary capillaries, along with intraalveolar
hemorrhage and
fibrin deposition. In animals protected with
apolactoferrin,
deferoxamine mesylate, or
dimethyl sulfoxide, the morphological studies reveal leukoaggregates but no endothelial cell damage,
hemorrhage, or
fibrin deposition. These data support the concept that tissue injury that is
complement and neutrophil dependent may be related to generation of
OH. derived from H2O2 after leukocytic activation.