SICKLE ERYTHROCYTES INDUCE PROSTACYCLIN AND THROMBOXANE SYNTHESIS BY ISOLATED-PERFUSED RAT LUNGS

The role of eicosanoids in the pathogenesis of acute or chronic lung s yndrome in sickle cell disease is unknown. We investigated the synthes is of prostacyclin (PGI(2)), thromboxane (Tx) A(2), and prostaglandin (PG) E(2) by three groups of isolated rat lungs perfused with buffer ( GPBS), normal (HbAA), and sickle (HbSS) erythrocyte suspensions. Isola ted lungs were perfused at a constant pressure and flow rate (Q) of 40 ml.kg(-1).min(-1) with GPBS or 7% erythrocyte suspensions for 15 min. Autologous platelet-rich plasma (PRP) was added, and perfusion was co ntinued for 15 min and then at two times Q for another 15 min. Perfusa te samples were assayed for the specific eicosanoids. Perfusate level of PGI(2) in GPBS lungs was the least among the three groups. However, the PGI(2) level in HbSS lungs was 90% higher than from HbAA lungs af ter 15 min of perfusion and was 180% higher on perfusion with PRP. Add itionally, coperfusion of erythrocytes and PRP augmented perfusate lev els of TxA(2) and PGE(2) over 1,000% more in HbSS than HbAA lungs. The se data show that HbSS erythrocytes increased perfusate levels of the eicosanoids, suggesting increased synthesis, perhaps due to aberrant e rythrocyte-endothelium interactions.