Genichi Nasu

Role of pulmonary intravascular macrophages activation in increased pulmonary microvascular permeability.

Pulmonary intravascular macrophages reside in the alveolar capillaries of sheep lung. We tested the effects of pulmonary intravascular mcrophages activation on pulmonary microvascular permeability.Sheep were divided into 3 groups; latex group, indomethacin group and OKY-046 (thromboxane A2 synthetase inhibitor) group. In each group, we infused latex beads emulsion, 1 μm in diameter, 5.46×1010 beads/kg, intraarterially. In latex group, lymph protein clearance increased significantly during and after the infusion period. In indomethacin group, increases in lymph protein clearance were blocked completely. However, in OKY-046 group, lymph protein clearance increased significantly 3 hours after the infusion period. In each group, peripheral white blood cell counts decreased significantly during the infusion period, and recovered to the baseline valeus after the infusion. Many latex beads were caught by pulmonary intrvascular macrophages selectively.These results suggest that pulmonary intravascular macrophages activation through their phagocytic uptake of microparticles is essential to increase in pulmonary microvascular permeability in sheep.

Role of neutrophil migration on increased pulmonary microvascular permeability.

The precise role of neutrophils in adult respiratory distress syndrome is not yet clear. Endotoxin administration is known to induce the permeability pulmonary edema with neutrophil migration into alveolar spaces. Leukotriene B4 is known as a strong chemotactic factor. To clearify the roles of neutrophils on pulmonary microvascular injury, we compared the effects of endotoxin and leukotriene B4 on lung lymph dynamics and neutrophil migration. Endotoxin caused increase in microvascular permeability and migration of neutrophils into alveolar spaces.Whereas leukotriene B4 did not affect lung microvascular permeability. Neutrophils in broncho-alveolar lavage fluid after leukotriene B4 administration increased to the same value as which after endotoxin administration. These results suggest that the neutrophil migration into alveolar spaces is not essential to develop the permeability pulmonary edema.