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.
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.
Dvorak
A M
AM
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
Tepper
R I
RI
Weller
P F
PF
Morgan
E S
ES
Estrella
P
P
Monahan-Earley
R A
RA
Galli
S J
SJ
D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001762:Blepharitis / Q000378:metabolism / Q000473:pathology*; D015550:Cell Degranulation; D005143:Eyelids / Q000378:metabolism / Q000648:ultrastructure*; D006636:Histamine Release; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D012701:Serotonin / Q000378:metabolism
D015847:Interleukin-4; D012701:Serotonin; D006631:Amine Oxidase (Copper-Containing)