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Generation of leukotrienes by human monocytes pretreated with cytochalasin B and stimulated with formyl-methionyl-leucyl-phenylalanine

Journal Article · · J. Immunol.; (United States)
OSTI ID:6936480
The N-formylated tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) initiated the generation of immunoreactive C-6 sulfidopeptide leukotrienes and of leukotriene B/sub 4/ (LTB/sub 4/) in a dose-dependent manner from monolayers of human monocytes pretreated for 10 min with 5 ..mu..g/ml of cytochalasin B. The maximal response to FMLP occurred within 10 min, and the sum of the two classes of leukotrienes generated was about 1/6 that obtained from monocytes stimulated with calcium ionophore A23187. The requirement for cytochalasin B in order for FMLP, but not the calcium ionophore, to stimulate leukotriene generation is compatible with the ability of cytochalasin B to augment in other cells certain stimulus-specific transmembrane responses that are not dependent on the integrity of the cytoskeleton. Resolution by reverse phase high performance liquid chromatography of the products released from monocytes pretreated with cytochalasin B and stimulated with FMLP or calcium ionophore yielded a single peak of immunoreactive LTB/sub 4/ eluting at the same retention time as the synthetic standard. The leukotriene-generating response of monolayers of human monocytes pretreated with cytochalasin B to FMLP is receptor-mediated, as indicated by the inactivity of the structural analog N-acetyl-methionyl-leucyl-phenylalanine and by the capacity of the FMLP receptor antagonist carbobenzoxyphenylalanyl-methionine to inhibit the agonist action of FMLP in a dose-response fashion.
Research Organization:
Harvard Medical School, Boston, MA
OSTI ID:
6936480
Journal Information:
J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 136:2; ISSN JOIMA
Country of Publication:
United States
Language:
English