ANNEXIN-I CONCENTRATION AND PROSTACYCLIN PRODUCTION IN RAT LONG AND ALVEOLAR MACROPHAGES FOLLOWING IRRADIATION

The purpose of this study was to gather additional evidence in irradia ted rat lung on the relationship between annexin I and prostaglandin s ynthesis. The right hemithorax of the animal was exposed to a single d ose of 0 or 30 Gy of X-rays, and the animals were killed 3 months post irradiation. Levels of annexin I and synthesis of prostacyclin (PGI(2) ) were determined in lungs, in cell-free bronchoalveolar lavage (BAL) fluid, and in macrophages ravaged from those lungs. In addition, prote in concentration, lactate dehydrogenase (LDH) activity and macrophage count in BAL fluid obtained from irradiated lung were compared with th at from sham-irradiated (0 Gy) lung. Levels of annexin I, the putative inhibitor of phospholipase A(2), in lung and cell-free BAL fluid were decreased in samples from irradiated animals. By contrast, the level of annexin I in macrophages lavaged from irradiated lung was higher th an that in macrophages from sham-irradiated lung. The irradiated lung produced nearly 3.5 times more prostacyclin than did the control lung. However, prostacyclin synthesis by macrophages lavaged from irradiate d lung was no different than that of macrophages from sham-irradiated lung. Protein, LDH and macrophage number in BAL fluid from irradiated lungs were significantly higher than in corresponding specimens from s ham-irradiated lungs. These data demonstrate that reduced levels of an nexin I, as well as increased protein concentration, LDH activity and macrophage numbers in irradiated rat lung are reflected in BAL fluid. Therefore, information obtained from BAL fluid, but not from BAL macro phages, reflects lung status, and may serve as a minimally invasive in dex of radiation pneumonitis in this model. In irradiated lung, increa sed PGI(2) synthesis coupled with a decreased annexin I level are cons istent with the hypothesis of an inhibitory role of annexin I in prost aglandin metabolism. However, this hypothesis is not supported by find ings in BAL macrophages, where increased annexin I concentration is no t accompanied by a decrease in PGI(2) production. In view of the latte r findings, and a previous study from our laboratory demonstrating tha t phospholipase activity in irradiated rat lung is in fact decreased, despite the reduction in annexin I concentration and the hyperproducti on of prostanoids, it would seem unlikely that annexin I negatively mo dulates prostaglandin synthesis via inhibition of phospholipase in thi s model.