Release of platelet-activating factor (PAF-acether) and arachidonic acid metabolites from alveolar macrophages

Human, monkey and rat alveolar macrophages (AM) release PAF-acether in a dose-dependent fashion in the presence of 1 to 5 microgram/ml ionophore A 23187 (2.5 pmol of PAF-acether from 2.5 x 10(5) cells) but not in the presence of zymosan. Arachidonic acid (AA) metabolites released from AM from these species were studied. Thromboxane A2 TxA2) - detected by its action on rabbit arteries - was released from human, monkey and rat AM upon addition of 0.5 mM AA. This release was inhibited by aspirin and indomethacin. Lipoxygenase and cyclooxygenase AA metabolites from rat AM were identified using high efficiency glass capillary column gas chromatography coupled to mass spectrometry. The cyclooxygenase metabolites PGF2 alpha, E2 and D2 and TxB2 were identified. The lipoxygenase-dependent AA metabolites were explored using aspirin-pretreated AM. Only 12 HETE was found. These data indicate that AM secrete several substances with bronchoconstrictive activity: PGF2 alpha, D2, TxA2 and PAF-acether. Therefore an active role of AM in human and experimental bronchoconstriction must be considered.