BRYOSTATINS TRIGGER HUMAN POLYMORPHONUCLEAR NEUTROPHIL AND MONOCYTE OXIDATIVE-METABOLISM - ASSOCIATION WITH IN-VITRO ANTINEOPLASTIC ACTIVITY

Bryostatin-1 - but not bryostatin-13 - a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, triggered human polymorphonu clear neutrophil (PMN) and monocyte release of reactive oxygen radical s, as measured by the generation of lucigenin chemiluminescence and by the ferricytochrome c reduction assay. The release of oxygen radicals by bryostatins was sensitive to inhibitors of protein kinases, but re sistant to the inhibition of phospholipase A, activity and arachidonic acid metabolism (prior treatment with mepacrine or indomethacin). Com parison of the effect of protein kinase (PK) inhibitors H-8, H-7 and s taurosporine on bryostatin-1-induced neutrophil oxygen radical release further suggested a requirement for activation of phospholipid-depend ent PKC, but not for cGMP- or cAMP-dependent pK. In cytostatic assays, PMNs treated with bryostatin-l inhibited the growth of the erythroleu kaemic cell line K562 in a concentration-dependent manner. These findi ngs suggest that the reported antineoplastic effect of bryostatins may result, at least in part, from activation of PMNs and monocytes.