Endogenous and exogenous catalase in reoxygenation lung injury

Abstract

Reexpansion pulmonary edema parallels reperfusion (reoxygenation) injuries in other organs in that hypoxic and hypoperfused lung tissue develops increased vascular permeability and neutrophil infiltration after reexpansion. This study investigated endogenous lung catalase activity and H2O2 production during hypoxia (produced by lung collapse) and after reoxygenation (resulting from reexpansion), in addition to assessing the effects of exogenous catalase infusion on the development of unilateral pulmonary edema after reexpansion. Lung collapse resulted in a progressive increase in endogenous catalase activity after 3 (14%) and 7 days (23%), while activities in contralateral left lungs did not change (normal left lungs averaged 180 +/- 11 units/mg DNA). Tissue from control left lungs released H2O2 into the extracellular medium at a rate calculated to be 242 +/- 34 nmol.h-1.lung-1. No significant change in extracellular release of H2O2 occurred after 7 days of right lung collapse. However, after reexpansion of the previously collapsed right lungs for 2 h, H2O2 release from both reexpanded right and contralateral left lungs significantly increased (88 and 60%, respectively) compared with controls. Infusion of exogenous catalase significantly increased plasma and lung catalase activities. Exogenous catalase infusion prevented neither the increase in lung permeability nor the infiltration with neutrophils that typically occurs in reexpanded lungs. These data indicate that lung hypoxia/reoxygenation, induced by sequential collapse and reexpansion, has specific effects on endogenous lung catalase activity and H2O2 release. However, exogenous catalase does not prevent reexpansion pulmonary edema, eliminating extracellular (but not intracellular) H2O2 as an important mediator of unilateral lung injury in this model.

Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo

“…Only Cremer et al (12) found a limitation of pulmonary reperfusion injury by giving the oxygen free radical scavengers in combination of catalase and superoxide dismutase during perfusion and continuously during the first 20 min in a canine model of heterotopic heart-lung transplantation. The main inability of exogenous catalase administration to provide beneficial physiological effects lies in the specific effects of endogenous lung catalase activity (25). Catalase is localized in the intracellular compartment.…”

“…Several attempts to limit I/R injury have been employed, e.g., elimination of neutrophil granulocytes (an important source of ROS generation) and/or maximization of antioxidative capacity under supply of antioxidative enzymes, vitamins, and others (23,24,46). The results, however, have been inconsistent (12,25,26,47). This might be because of insufficient uptake into the endothelial cells (10,25).…”

“…The results, however, have been inconsistent (12,25,26,47). This might be because of insufficient uptake into the endothelial cells (10,25). Therefore, the objective of our current investigation was to deliver antioxidant enzymes to the pulmonary endothelium by immunotargeting of lung-specific endothelial antigens (34).…”

Pre-ischaemic conditioning of the pulmonary endothelium by immunotargeting of catalase via angiotensin-converting-enzyme antibodies☆☆☆

“…Only Cremer et al demonstrated a diminished pulmonary reperfusion injury in a canine model of heterotopic heart-lung transplantation by using a combination of catalase and superoxide dismutase administered during flush-perfusion and the first 20 min of reperfusion [19]. The main inability of exogenous catalase administration to provide beneficial physiologic effects lies in the specific physical location of endogenous lung catalase activity [21]. Catalase is localised to the intracellular compartment and Muzykantov et al have shown that biotinylated catalase has a poor uptake into the intracellular compartment of the pulmonary endothelium [22].…”

Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung

“…Consistent with that idea, it is known that the interaction between adherent neutrophils and endothelial cells regulates lung permeability in RPE (10) and that reactive oxygen species (ROS) produced by neutrophils increase pulmonary endothelial permeability. On the other hand, using an animal RPE model Jackson et al (14) found that exogenous catalase does not prevent RPE, which eliminates extracellular hydrogen peroxide as an important contributor, but they did detect endogenous lung catalase activity and hydrogen peroxide release. This supports the idea that endogenous production of ROS is a key contributor to RPE.…”