International Journal of Clinical and Medical Education Research(IJCMER)
ISSN: 2832-7705 | DOI: 10.33140/IJCMER
Impact Factor: 0.93
Short Communication - (2025) Volume 4, Issue 4
Signal Transduction of Nerve Growth Factor Induced Histamine Secretion from Mast Cells
Received Date: Jun 22, 2025 / Accepted Date: Jul 17, 2025 / Published Date: Jul 24, 2025
Copyright: ©2025 Ilonka Ferjan. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Ferjan, I. (2025). Signal Transduction of Nerve Growth Factor Induced Histamine Secretion from Mast Cells. Int J Clin Med Edu Res, 4(4), 01-02.
Abstract
Mast cells play a central role in allergic reactions. In response to immunologic or non-immunologic stimuli they release many inflammatory mediators. Biogenic amine, histamine is one of the essential mediator, which is relesed from mast cells during inflammation reactions. Nerve growth factor (NGF) is essetial for the survival of various neurones and has significant role in inflammation and allergic reactions. Histamine release from mast cells induced by NGF is strongly dependent on the concentration of extracellular Na+and Ca2+ ions. The studies of the role of different enzymes in NGF induced histamine relese have shown that tyrosine kinase, phosphatidylinositol-3-kinase, protein kinase C and phospholipase C are involved in the signal transduction responsible for NGF induced histamine secretion from mast cells. The right ionic composition of the extracellular fluid and the exact signaling pathway involved in NGF induced histamin secretion indicate the importance of NGF in various inflammatory and allergic deseases.
Keywords
Nerve Growth Factor, Mast Cells, Histamine Release, Mechanism of Action
Abbreviations
NGF: Nerve Growth Factor
TrKA Receptor: Tyrosine Kinase A Receptor
Introduction
Mast cells play a central role in allergic reactions. In response to immunologic or non-immunologic stimuli they release many inflammatory mediators [1]. Biogenic amine, histamine is one of the essential inflammatory mediator, which is released from mast cells during inflammation and allergic reactions. The stimmulation of histamine release from mast cells can be induced by an immunologic or non-immunologic stimuli. The mechanism of non-immunological induced histamine relese is different from that induced by the immunologic stimuli [2]. Nerve growth factor (NGF) is essential for the survival of several neurones and has a wide range of other effects [2,3]. Among these effects, NGF can induce degranulation of mast cells by interacting with its highaffinity receptor of a TrkA-type [2]. Since elevated levels of NGF in fluids of patients with allergic diseases have been reported, it can play an important role in allergic reactions [4]. Therefore, it is of interest to study the mechanism of the secretory process induced by NGF. Basic secretagogue, compound 48/80 is used as a standard for non-immunological trigger of secretion process from mast cells. The signal trunsduction pathway involved in histamine release from mast cells provoked by NGF can be compared with the secretion induced by basic secretagogue compound 48/80.
The Effect of Ionic Composition of the Medium in Histamine Relese Process Induced by Different Stimuli.
The secretion of mediators from mast cells induced by immunologic or by non-immunologic stimuli is strongly dependent on the presence of Ca2+ ions. Stimmulation of mast cells by an imunologic stimuli and by NGF require the presence of extracellular calcium to induce histamine release [5]. However, the relese induced by compound 48/80 is not strongly dependent on the presence of extracellular calcium [5]. These findings show that some different steps are involved in the secretion process induced either by NGF or by compound 48/80. Beside the importance of extracellular Ca2+ in the secretion process, extracellular Na+ ions play also an important role in the secretion of the inflammatory mediators [6].
Sodium-free medium potentiates NGF induced histamine relese [7]. Similar potentiation of histamine release in sodium free medium occurs also by stimmulation of mast cells either by compound 48/80 or by the immunologic stimuli [7,8]. Since, amiloride, an inhibitor of Na+Ca2+ exchanger abolish this effect, Na+Ca2+ exchanger might have a role in changing the concentration of Na+ and Ca2+ ions [5]. In the medium containing low concentratins of Na + ions, Na+Ca2+ exchanger of mast cells exchanges extracellular Ca2+ ions for intracellular Na+ ions [7]. Therefore the influx of Ca2+ ions in the cell occurs [9]. Conseqvently, the increased intracellular free calcium concentration leads to the potentiation of histamine release induced by various stimuli [10].
The Regulation of Histamine Release by Various Enzymes
Various enzymes are required in the signal transduction of histamine secretion induced by NGF and compound 48/80. Tyrosine kinase, phospholipase C and proteinkinase C are involved in the signal trunduction pathway induced by both secretagogues [10]. However, phosphatidylinositol-3-kinase is activated only in NGF mediated degranulation process [10]. This indicates that NGF triggers histamine secretion by a specific mechanism, which differs from that induced by compound 48/80. However, the same enzymes are needed in the secretory process induced either by NGF or by IgE stimmulation [11]. These findings suggest that similar pathways may be involved in the secretion induced either by NGF or by IgE stimmulation. The right ionic composition of the extracellular fluid and the exact signaling pathway involved in NGF induced histamin secretion indicate the importance of NGF in various inflammatory and allergic deseases.
References
- Moller, A., Grabbe, J., & Czarnetzki, B. M. (1991). Mast cells and their mediators in immediate and delayed immune reactions. Skin Pharmacol, 4(Suppl 1), 56-63.
- Minnone, G., De Benedetti, F., & Bracci-Laudiero, L. (2017). NGF and its receptors in the regulation of inflammatory response. International journal of molecular sciences, 18(5), 1028.
- Skaper, S. D. (2017). Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology, 151(1), 1-15.
- Frossard, N., Freund, V., Advenier, C. (2004). Nerve growth factor and its receptors in astma and inflammation. Eur J Pharmacol 500, 453-65.
- Štempelj, M., sarman-Krzan, M., & Ferjan, I. (2003). Regulatory role of extracellular Na+ and Ca2+ ions in nerve growth factor induced histamine secretion from rat mast cells. Inflammation Research, 52(2), 74-78.
- Smith, T. F., Sanchez-Legrand, F., McKean, L. P., Kutner, M. H., Cragoe Jr, E. J., & Eaton, D. C. (1992). Role of sodium in mediator release from human basophils. Journal of allergy and clinical immunology, 89(5), 978-986.
- Alfonso, A., Lago, J., Botana, M. A., Vieytes, M. R., & Botana,
- L. M. (1999). Characterization of the Na+/Ca2+ Exchanger on Rat Mast Cells: Evidence for a Functional Role on the Regulation of the Cellular Response. Cellular Physiology and Biochemistry, 9(2), 53-71.
- Rumpel, E., Pilatus, U., Mayer, A., & Pecht, I. (2000). Na+- Dependent Ca2+ Transport Modulates the Secretory Response to the FcÃz Receptor Stimulus of Mast Cells. Biophysical Journal, 79(6), 2975-2986.
- Bonini, S., Lambiase, A., Properzi, F., Bresciani, M., Sacerdoti, G., Bonini, S., & Aloe, L. (2002). Nerve growth factor and asthma. Allergy, 57, 13-15.
- Štempelj, M., & Ferjan, I. (2005). Signaling pathway in nerve growth factor induced histamine release from rat mast cells. Inflammation Research, 54(8), 344-349.
- Tedeschi, A., Lorini, M., Gibelli, S., & Miadonna, A. (2000). Effects of protein kinase C and phospholipase C inhibitors on IgE-dependent and IgE-independent basophil histamine release. Inflammation Research, 49(9), 480-485.