Lipid peroxidation and lung ultrastructural changes in an experimental model of leukocyte-mediated pulmonary injury

Abstract

The aim of this study was to study ultrastructural changes and lipid peroxidation in rabbits lung after massive complement activation and leukocyte aggregation. A prolonged and massive leukocyte activation was induced by intraperitoneal inoculation of zymosan suspected in paraffin. Fifteen animals (group 3) were given 0.6 g/kg of zymosan, 22 animals (group 2) received 1 g/kg, and 11 rabbits (group 1) were treated with paraffin alone and served as controls. An acute mortality rate of 40% was observed in group 3 and of 68% in group 2. Surviving animals were studied for 10 days. In these animals a marked decrease in circulating granulocytes and a progressive decline in arterial PO2 were recorded (PO2 on day 10 in group 2 animals was 51.94 +/- 4.26, p less than 0.01). Microscopic and ultrastructural evaluation revealed sequestration of granulocytes in the pulmonary microvasculature. Studies of lung homogenates demonstrated increased levels of lipid peroxide derivative malondialdehyde (group 2 rabbits, 1624 +/- 638; group 1, 795 +/- 57 pm/mg pt, p less than .001) and decreased levels of the tissue antioxidant alpha-tocopherol. The results of this study are compatible with the hypothesis of leukocyte-mediated injury through production of oxygen radicals.

Complement fragment C3a in plasma of asphyxiated neonates

“…Therefore, complement activation can be determined by measuring the presence of C3 split products [15]. Anaphylatoxins, especially C5a, exhibit immuneregulatory activity and can induce leucocyte aggregation with the subsequent release of hydrolytic enzymes, oxygen radicals and arachidonic acid metabolites, which contributes to an autodestructive inflammatory process affecting the endothelium [2,11,19,33]. These mechanisms are probably involved in the pathogenesis of ARDS and multiple organ failure [2,17,20].…”

“…Anaphylatoxins, especially C5a, exhibit immuneregulatory activity and can induce leucocyte aggregation with the subsequent release of hydrolytic enzymes, oxygen radicals and arachidonic acid metabolites, which contributes to an autodestructive inflammatory process affecting the endothelium [2,11,19,33]. These mechanisms are probably involved in the pathogenesis of ARDS and multiple organ failure [2,17,20]. Although many plasma factors have been studied extensively in experimental and clincial ARDS, C3a emerges as the superior predictor for ARDS in adult risk patients with polytrauma when compared to C5a, thromboxane B2, prostanglandins, neopterin, phospholipase A2 etc.…”