Pulmonary synthesis, release, and metabolism of prostaglandins.
Immunologic or calcium-dependent activation of proteolytically dispersed human lung cells containing 5% mast cells causes the release of large amounts of PGD2 and TxB2. In cell purification experiments, only those fractions containing mast cells had the capacity to generate PGD2 and release histamine with IgE-dependent activation. The cells of origin of T X B2 are likely to be cells of the monocyte-macrophage series, although additional eicosanoid release may occur from immunologically activated lymphocytes and eosinophils. In men who have asthma, inhalation of low concentrations of PGD2 results in bronchoconstriction, whereas higher concentrations of PGD2 are needed to produce bronchoconstriction in normal subjects. Subjects with asthma exhibited 3.5-fold greater responsiveness to inhaled PGD2 than to PGF2 alpha. These observations demonstrate that PGD2 is the most potent bronchoconstrictor prostanoid tested in man. In both normal subjects and subjects with asthma, a single inhalation of PGF2 alpha resulted in a doubling in plasma levels of 13,14-dihydro-15-keto-PGF2 alpha. Plasma levels of this metabolite did not change after PGD2 inhalation. These results indicate that the 11-keto reduction of PGD2 to PGF2 alpha with subsequent inactivation is not important in the initial metabolism of PGD2.
Robinson
C
C
Hardy
C C
CC
Holgate
S T
ST
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001249:Asthma / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D011464:Epoprostenol / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D011453:Prostaglandins; D007073:Immunoglobulin E; D000001:Calcimycin; D013928:Thromboxane A2; D011464:Epoprostenol