The antineoplastic bryostatins affect human basophils and mast cells differently

V. Patella, V. Casolaro, A. Ciccarelli, George Pettit, M. Columbo, G. Marone

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multipotential 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 (t 1/2 ± SEM = 38.2 ± 4.7 minutes v 8.9 ± 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37°C, approximately 30% less at 30°C, and no release at 22°C or 4°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.

Original languageEnglish (US)
Pages (from-to)1272-1281
Number of pages10
JournalBlood
Volume85
Issue number5
StatePublished - 1995
Externally publishedYes

Fingerprint

Bryostatins
Basophils
Mast Cells
Antineoplastic Agents
Histamine
Histamine Release
Interleukin-3
Tetradecanoylphorbol Acetate
Skin
Leukotriene C4
Lung
Tissue
Macrophage Colony-Stimulating Factor
Staurosporine
Protein C Inhibitor
Colony-Stimulating Factors
Lactones
Granulocyte Colony-Stimulating Factor
Protein Kinase Inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor

ASJC Scopus subject areas

  • Hematology

Cite this

Patella, V., Casolaro, V., Ciccarelli, A., Pettit, G., Columbo, M., & Marone, G. (1995). The antineoplastic bryostatins affect human basophils and mast cells differently. Blood, 85(5), 1272-1281.

The antineoplastic bryostatins affect human basophils and mast cells differently. / Patella, V.; Casolaro, V.; Ciccarelli, A.; Pettit, George; Columbo, M.; Marone, G.

In: Blood, Vol. 85, No. 5, 1995, p. 1272-1281.

Research output: Contribution to journalArticle

Patella, V, Casolaro, V, Ciccarelli, A, Pettit, G, Columbo, M & Marone, G 1995, 'The antineoplastic bryostatins affect human basophils and mast cells differently', Blood, vol. 85, no. 5, pp. 1272-1281.
Patella V, Casolaro V, Ciccarelli A, Pettit G, Columbo M, Marone G. The antineoplastic bryostatins affect human basophils and mast cells differently. Blood. 1995;85(5):1272-1281.
Patella, V. ; Casolaro, V. ; Ciccarelli, A. ; Pettit, George ; Columbo, M. ; Marone, G. / The antineoplastic bryostatins affect human basophils and mast cells differently. In: Blood. 1995 ; Vol. 85, No. 5. pp. 1272-1281.
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abstract = "Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multipotential 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 (t 1/2 ± SEM = 38.2 ± 4.7 minutes v 8.9 ± 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37°C, approximately 30{\%} less at 30°C, and no release at 22°C or 4°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.",
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AU - Marone, G.

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N2 - Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multipotential 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 (t 1/2 ± SEM = 38.2 ± 4.7 minutes v 8.9 ± 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37°C, approximately 30% less at 30°C, and no release at 22°C or 4°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.

AB - Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multipotential 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 (t 1/2 ± SEM = 38.2 ± 4.7 minutes v 8.9 ± 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37°C, approximately 30% less at 30°C, and no release at 22°C or 4°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.

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