Akira Aida

Role of pulmonary intravascular macrophages in anti-platelet serum-induced pulmonary hypertension in sheep

It has been reported that an injection of anti-sheep platelet serum (AsPS) induces transient pulmonary hypertension in sheep, but the mechanism by which this occurs has not been well explained. To examine the hypothesis that pulmonary intravascular macrophages (PIMs) are involved in this phenomenon, we investigated the morphological features of PIMs from sheep that received three different kinds of AsPS injections. The pulmonary arterial pressure response was examined not only in sheep that have many PIMs in the lung and had received AsPS, but also in rats that reportedly have few PIMs and had received an injection of anti-rat platelet serum. The pulmonary arterial pressure responses of the two species were quite different in quality and quantity. In sheep whose pressure response was definitely positive in association with production of thromboxane in the pulmonary circulation, PIMs were found by fluorescent microscopy and electron microscopy to phagocytize aggregated platelets that bound AsPS. These results suggest that PIMs significantly contribute to AsPS-induced transient pulmonary hypertension in sheep.

Effects of platelet depletion on PMA-induced acute lung injury in awake sheep

Little is known about the role of circulating platelets in PMA-induced lung injury in vivo. We investigated the effects of platelet depletion (PD) on the injury using seven unanesthetized sheep with lung lymph fistulas and eight other sheep for morphological study. PD diminished a decrease in the lymph to plasma concentration ratio (L/P) after 1 microgram/kg PMA treatment (n = 4) and caused more increases in lung lymph flow, L/P and lung lymph clearance after 5 micrograms/kg PMA treatment (n = 3) than in control sheep. The high dose was lethal to platelet-depleted sheep. However, PD had no effects on pulmonary hemodynamics. Morphologically, alveolar hemorrhages and exudate, and bleb formation of type I epithelial cells were more prominent in the platelet-depleted sheep than in the control sheep. We conclude that circulating platelets have protective effects against PMA-induced lung injury but have little involvement in PMA-induced pulmonary hypertension.