Nerve growth factor influences IgE-mediated human basophil activation: functional properties and intracellular mechanisms compared with IL-3.
NGF and IL-3 play a unique role in supporting human basophil differentiation and mediator secretion. Their importance in allergic disease is underlined further by studies showing elevated levels of these factors in asthmatics. Here, we compared the abilities of IL-3 and NGF to stimulate basophil histamine, IL-4 or IL-13 release, either directly or in conjunction with IgE-dependent stimulation and assessed the intracellular signals responsible. Our results show that the ability of IL-3 and NGF to enhance IgE-dependent histamine release are similar. Both factors also potentiated IgE-dependent IL-13 secretion to a greater degree than the release of histamine or IL-4. At high concentrations (100 ng/ml), IL-3 and NGF alone were capable of releasing cytokines but little histamine. These abilities of IL-3 and NGF to modulate basophil activation were sensitive to blockade by specific inhibitors of PI 3-kinase, p38 MAPK and PLC, but not PKC, suggesting that their effects are mediated considerably by pathways comparable to IgE-dependent signalling.
Gibbs
Bernhard F
BF
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. bfgibbs@gmx.de
Zillikens
Detlef
D
Grabbe
Jürgen
J
D001491:Basophils / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000276:immunology / Q000502:physiology*; D020932:Nerve Growth Factor / Q000502:physiology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007377:Interleukin-3; D007073:Immunoglobulin E; D020932:Nerve Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases