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Cytokine-induced protein tyrosine phosphorylation is essential for cytokine priming of human eosinophils.
J Allergy Clin Immunol. 1998 Jan; 101(1 Pt 1):103-9.JA

Abstract

BACKGROUND

Human eosinophils are strongly modulated by the eosinophilotrophic cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). A clear intracellular effect of these cytokines is the induction of tyrosine phosphorylation of multiple cellular substrates. However, the relevance of tyrosine phosphorylation for eosinophil functioning has not been established.

OBJECTIVE

In this study we have investigated dose-response and time curves of IL-5-, IL-3-, and GM-CSF-induced tyrosine phosphorylation in eosinophils. Moreover, we have evaluated the importance of IL-5-induced tyrosine phosphorylation for priming of human eosinophils.

METHODS

Cytokine-induced tyrosine phosphorylation was monitored on western blot with an antiphosphotyrosine antibody (4G10). To probe the relevance of tyrosine phosphorylation for priming, eosinophils were primed with IL-5 in the presence of the tyrosine kinase inhibitor herbimycin A. Platelet activating factor (PAF) was used as a control priming agent. Subsequently, the eosinophils were incubated with serum-treated zymosan (STZ) to activate the respiratory burst. Binding of STZ was determined by FACS analysis.

RESULTS

IL-5-, IL-3-, and GM-CSF-induced tyrosine phosphorylation was found at concentrations that primed eosinophil effector mechanism (median effective dose values: approximately 5.10(-11) mol/L, approximately 5.10(-10) mol/L, and approximately 5.10(-12) mol/L for IL-5, IL-3, and GM-CSF, respectively). Cytokine-induced tyrosine phosphorylation was transient with an optimum value at 15 minutes. IL-5 priming of STZ-induced activation of the respiratory burst was blocked by herbimycin A, whereas PAF still primed this response. In fact, herbimycin A inhibited IL-5 priming of STZ binding to human eosinophils. On the other hand, PAF priming of STZ binding was not affected by herbimycin A. Both IL-5-induced and PAF-induced tyrosine phosphorylation were inhibited by herbimycin A.

CONCLUSION

These data demonstrate for the first time that IL-5 priming of opsonized particle-induced responses is mediated by tyrosine kinase activity in human eosinophils.

Authors+Show Affiliations

Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9449508

Citation

van der Bruggen, T, et al. "Cytokine-induced Protein Tyrosine Phosphorylation Is Essential for Cytokine Priming of Human Eosinophils." The Journal of Allergy and Clinical Immunology, vol. 101, no. 1 Pt 1, 1998, pp. 103-9.
van der Bruggen T, Kanters D, Tool AT, et al. Cytokine-induced protein tyrosine phosphorylation is essential for cytokine priming of human eosinophils. J Allergy Clin Immunol. 1998;101(1 Pt 1):103-9.
van der Bruggen, T., Kanters, D., Tool, A. T., Raaijmakers, J. A., Lammers, J. W., Verhoeven, A. J., & Koenderman, L. (1998). Cytokine-induced protein tyrosine phosphorylation is essential for cytokine priming of human eosinophils. The Journal of Allergy and Clinical Immunology, 101(1 Pt 1), 103-9.
van der Bruggen T, et al. Cytokine-induced Protein Tyrosine Phosphorylation Is Essential for Cytokine Priming of Human Eosinophils. J Allergy Clin Immunol. 1998;101(1 Pt 1):103-9. PubMed PMID: 9449508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine-induced protein tyrosine phosphorylation is essential for cytokine priming of human eosinophils. AU - van der Bruggen,T, AU - Kanters,D, AU - Tool,A T, AU - Raaijmakers,J A, AU - Lammers,J W, AU - Verhoeven,A J, AU - Koenderman,L, PY - 1998/2/4/pubmed PY - 1998/2/4/medline PY - 1998/2/4/entrez SP - 103 EP - 9 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 101 IS - 1 Pt 1 N2 - BACKGROUND: Human eosinophils are strongly modulated by the eosinophilotrophic cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). A clear intracellular effect of these cytokines is the induction of tyrosine phosphorylation of multiple cellular substrates. However, the relevance of tyrosine phosphorylation for eosinophil functioning has not been established. OBJECTIVE: In this study we have investigated dose-response and time curves of IL-5-, IL-3-, and GM-CSF-induced tyrosine phosphorylation in eosinophils. Moreover, we have evaluated the importance of IL-5-induced tyrosine phosphorylation for priming of human eosinophils. METHODS: Cytokine-induced tyrosine phosphorylation was monitored on western blot with an antiphosphotyrosine antibody (4G10). To probe the relevance of tyrosine phosphorylation for priming, eosinophils were primed with IL-5 in the presence of the tyrosine kinase inhibitor herbimycin A. Platelet activating factor (PAF) was used as a control priming agent. Subsequently, the eosinophils were incubated with serum-treated zymosan (STZ) to activate the respiratory burst. Binding of STZ was determined by FACS analysis. RESULTS: IL-5-, IL-3-, and GM-CSF-induced tyrosine phosphorylation was found at concentrations that primed eosinophil effector mechanism (median effective dose values: approximately 5.10(-11) mol/L, approximately 5.10(-10) mol/L, and approximately 5.10(-12) mol/L for IL-5, IL-3, and GM-CSF, respectively). Cytokine-induced tyrosine phosphorylation was transient with an optimum value at 15 minutes. IL-5 priming of STZ-induced activation of the respiratory burst was blocked by herbimycin A, whereas PAF still primed this response. In fact, herbimycin A inhibited IL-5 priming of STZ binding to human eosinophils. On the other hand, PAF priming of STZ binding was not affected by herbimycin A. Both IL-5-induced and PAF-induced tyrosine phosphorylation were inhibited by herbimycin A. CONCLUSION: These data demonstrate for the first time that IL-5 priming of opsonized particle-induced responses is mediated by tyrosine kinase activity in human eosinophils. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/9449508/Cytokine_induced_protein_tyrosine_phosphorylation_is_essential_for_cytokine_priming_of_human_eosinophils_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(98)70200-3 DB - PRIME DP - Unbound Medicine ER -