title: Sickle erythrocytes induce prostacyclin and thromboxane synthesis by isolated perfused rat lungs.
abstract: The role of eicosanoids in the pathogenesis of acute or chronic lung syndrome in sickle cell disease is unknown. We investigated the synthesis of prostacyclin (PGI2), thromboxane (Tx) A2, and prostaglandin (PG) E2 by three groups of isolated rat lungs perfused with buffer (GPBS), normal (HbAA), and sickle (HbSS) erythrocyte suspensions. Isolated lungs were perfused at a constant pressure and flow rate (Q) of 40 ml x kg(-1) x min(-1) with GPBS or 7% erythrocyte suspensions for 15 min. Autologous platelet-rich plasma (PRP) was added, and perfusion was continued for 15 min and then at two times Q for another 15 min. Perfusate samples were assayed for the specific eicosanoids. Perfusate level of PGI2 in GPBS lungs was the least among the three groups. However, the PGI2 level in HbSS lungs was 90% higher than from HbAA lungs after 15 min of perfusion and was 180% higher on perfusion with PRP. Additionally, coperfusion of erythrocytes and PRP augmented perfusate levels of TxA2 and PGE2 over 1,000% more in HbSS than HbAAlungs. These data show that HbSS erythrocytes increased perfusate levels of the eicosanoids, suggesting increased synthesis, perhaps due to aberrant erythrocyte-endothelium interactions.
authors.affiliation: Department of Pediatrics, University of California Los Angeles School of Medicine, Harbor-University of California Los Angeles Medical Center, Torrance 90502, USA.
authors.forename: B O
authors.initials: BO
authors.lastname: Ibe
authors.forename: J
authors.initials: J
authors.lastname: Morris
authors.forename: J
authors.initials: J
authors.lastname: Kurantsin-Mills
authors.forename: J U
authors.initials: JU
authors.lastname: Raj
mesh_terms: D000136:Acid-Base Equilibrium; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis*
chemical_list: D013928:Thromboxane A2; D011464:Epoprostenol; D015232:Dinoprostone