Localization of interleukin (IL) -4 but not IL-5 to human mast cell secretory granules by immunoelectron microscopy
Article first published online: 24 DEC 2001
Clinical & Experimental Allergy
Volume 30, Issue 4, pages 493–500, April 2000
How to Cite
Wilson, Shute, Holgate, Howarth and Bradding (2000), Localization of interleukin (IL) -4 but not IL-5 to human mast cell secretory granules by immunoelectron microscopy. Clinical & Experimental Allergy, 30: 493–500. doi: 10.1046/j.1365-2222.2000.00756.x
- Issue published online: 24 DEC 2001
- Article first published online: 24 DEC 2001
- electron microscopy;
- human mast cells;
Human mast cells synthesize and secrete many cytokines of relevance to the pathogenesis of allergic diseases such as asthma and rhinitis. In particular, interleukin (IL) -4 and IL-5 are likely to play key roles in the development of the inflammatory response that characterizes these diseases. Immunohistochemical studies on human nasal and bronchial mucosal biopsies suggest that IL-4 and IL-5 may be stored preformed in mast cells.
To identify whether IL-4 and IL-5 are stored within mast cell secretory granules.
We used immunogold electron microscopic analysis on bronchial mucosa and lung parenchyma from resected lung specimens, and a nasal mucosal biopsy from a patient with active allergic rhinitis. Samples were fixed in 4% paraformaldehyde plus 0.5% glutaraldehyde and processed into Lowicryl K4M resin by the ‘Progressive Lowering of Temperature’ technique. Ultrathin sections were stained immunohistochemically by an indirect immunogold method.
Immunoreactivity for IL-4, but not IL-5, was localized to the granules of mast cells in all tissue samples. IL-5 was localized to the matrix of eosinophil granules in these samples, but neither cytokine was detected in T cells. IL-4 immunoreactivity increased in the granules of mast cells 24 h after immunoglobulin (Ig) E-dependent activation (mean 17.5 ± 1.4 gold particles per granule) compared with nonactivated mast cells (mean 6.8 ± 0.8 gold particles per granule, P < 0.001), suggesting replenishment of stores by newly generated protein. Immunoreactive IL-5 remained undetectable in mast cells 24 h after activation, a time point at which they are known to secrete large quantities of this cytokine.
Human mast cells store IL-4 within the matrix of their granules. Very few, if any, lung or nasal mast cells store IL-5. A store of preformed IL-4 within mast cell granules is likely to have an important influence during the initiation and maintenance of the allergic immunological response.