Influence of chronic antigen exposure on the metabolism of PGH2 by microsomal preparations of airway and parenchymal tissues in the sheep.
The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized Ascaris suum antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A2, prostaglandin (PG) D2 and PGI2 from the PG endoperoxide intermediate, PGH2, was assayed over a range of substrate concentrations from 3-200 microM. Synthesis of PGI2 by trachealis microsomes was approximately 5-fold greater than that of TXA2. PGI2 and TXA2 production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA2 production predominated over PGI2 by 9-fold, preparations from Ascaris-exposed animals synthesized 50% more TXA2 than controls at PGH2 concentrations of 25 microM and above, whereas synthesis of PGI2 and PGD2 were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA2 and PGI2 in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA2 synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001200:Ascaris / Q000276:immunology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism*; D012756:Sheep; D013928:Thromboxane A2 / Q000096:biosynthesis; D014018:Tissue Distribution; D014132:Trachea / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D013928:Thromboxane A2; D011464:Epoprostenol