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The antineoplastic bryostatins affect human basophils and mast cells
differently
V Patella, V Casolaro, A Ciccarelli, GR Pettit, M Columbo and G Marone
Division of Clinical Immunology and Allergy, University of Naples Federico
II, School of Medicine, Italy.
Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina,
are potent antineoplastic agents and multi-potential stimulators of immune
cells. We have examined the effects of bryostatins on mediator release from
human basophilic leukocytes and human tissue mast cells. Bryostatins 1, 2,
and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and
unpurified peripheral blood basophils, whereas they caused no release of
peptide-leukotriene C4 from these cells. The rate of histamine release
caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/-
SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the
temperature dependence was similar (optimum release at 37 degrees C,
approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4
degrees C). The addition of increasing concentrations of extracellular Ca2+
to the medium caused histamine release in the presence of bryostatins.
Subeffective concentrations of bryostatins and anti-IgE produced a
synergistic effect on histamine release from basophils. Staurosporine,
chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein
kinase C inhibitors, inhibited the histamine secretion activated by
bryostatin 1 and tetradecanoylphorbol-acetate (TPA). Preincubation with
granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and
interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human
basophils induced by bryostatin 1. Neither bryostatin 1 nor bryostatin 2
induced the release of histamine from mast cells isolated from human lung
or skin tissues. However, brief (10 minutes) preincubation with bryostatin
1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by
anti-IgE from skin or lung mast cells. Bryostatin 1 was a more potent (by
approximately 30 times) inhibitor of IgE- mediated histamine release than
was TPA. The heterogeneous effects exerted by bryostatins on human
basophils and mast cells can be of interest for those designing therapeutic
trials using these agents.
Volume 85,
Issue 5,
pp. 1272-1281,
03/01/1995
Copyright © 1995 by The American Society of Hematology
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