Cyclooxygenase metabolites in human lung anaphylaxis: airway vs. parenchyma.
We studied the generation of arachidonic acid cyclooxygenase metabolites (AACMs) during in vitro anaphylaxis of passively sensitized human lung parenchymal and airway fragments. Prostaglandins E, F2 alpha, D2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 (PGE, PGF2 alpha, PGD2, 6-keto-PGF1 alpha, TXB2, respectively) were assayed by radioimmunoassay. Results with airway tissue were compared with subpleural parenchymal fragments from the same lungs similarly challenged. Spontaneous generation of prostacyclin (PGI2), as measured by its stable metabolite 6-keto-PGF1 alpha, exceeded by two- to threefold other spontaneous AACM release in both bronchial and parenchymal fragments. In airway antigen produced variable AACM responses, but in general the rank order was 6-keto-PGF1 alpha greater than PGE congruent to PGF2 alpha greater than PGD2 greater than TXB2. The rank for antigen-induced AACM release from parenchyma was 6-keto-PGF1 alpha congruent to PGD2 much greater than PGF2 alpha greater than TXB2 congruent to PGE. In airway, as in parenchyma, very little AACM production during anaphylaxis can be attributed to smooth muscle contraction per se. Histamine released from bronchi (0.67 +/- 0.30 micrograms/g lung) was significantly less than from parenchyma (3.7 +/- 0.70 micrograms/g) despite comparable histamine content. At comparable levels of histamine release, the parenchyma produced greater quantities than bronchi of all AACMs except PGE. The comparatively limited bronchial capacity to generate PGF2 alpha, PGD2, TXB2, and histamine (airway constrictors) along with predominant generation of PGI2 and PGE (airway relaxants) may help preserve airway patency.
D000707:Anaphylaxis / Q000378:metabolism*; D000941:Antigens / Q000276:immunology; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D011451:Prostaglandin-Endoperoxide Synthases