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Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of
interleukin-4 transgenic mice. Evidence of mast cell histamine release in
vivo by diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry
AM Dvorak, RI Tepper, PF Weller, ES Morgan, P Estrella, RA Monahan-Earley and SJ Galli
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
We used light and electron microscopy to analyze the eyelid inflammation
that develops in transgenic mice that overexpress interleukin-4 (IL-4;
Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained
plastic sections examined by light microscopy (Dvorak et al, J Exp Med
132:558, 1970), as well as by routine transmission electron microscopy,
indicated that the mast cells in the inflammatory eyelid lesions were
undergoing piecemeal degranulation, a form of secretion in which the cells'
cytoplasmic granules exhibit characteristic morphologic changes that are
thought to be associated with the prolonged, vesicle-mediated release of
the granules' constituents. Moreover, by using a newly reported enzyme
affinity-gold method, which stains histamine based on binding to diamine
oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show
that these activated mast cells had released much of their histamine
content. The eyelid lesions also exhibited increased numbers of mast cells;
interstitial fibrosis, particularly around cutaneous nerves and blood
vessels; activated fibroblasts; focal axonal damage; venules with
endothelial cells containing numerous vesiculo-vacuolar organelles; and
infiltrates of neutrophils and eosinophils. Our findings illustrate that
overexpression of the IL-4 gene in vivo can result in eyelid lesions
associated with piecemeal degranulation of mast cells, as well as tissue
fibrosis and a variety of other pathologic changes. These results also
represent the first direct morphologic evidence for histamine secretion by
mast cells in vivo.
Volume 83,
Issue 12,
pp. 3600-3612,
06/15/1994
Copyright © 1994 by The American Society of Hematology
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