Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation.
BACKGROUND
In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease.


OBJECTIVE
To determine the degranulation status of circulating eosinophils in common allergic diseases.


METHODS
Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM.


RESULTS
Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures).


CONCLUSIONS
In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.
Malm-Erjefält
M
M
Clinical and Experimental Pharmacology, Department of Laboratory Medicine, Lund University Hospital, University of Lund, Sweden. monika.malm-erjefalt@med.lu.se
Greiff
L
L
Ankerst
J
J
Andersson
M
M
Wallengren
J
J
Cardell
L-O
LO
Rak
S
S
Persson
C G A
CG
Erjefält
J S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000276:immunology; D029662:Betula / Q000276:immunology; D015550:Cell Degranulation; D015267:Churg-Strauss Syndrome / Q000097:blood; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D003876:Dermatitis, Atopic / Q000097:blood; D047150:Eosinophil Cationic Protein / Q000097:blood; D047209:Eosinophil Peroxidase / Q000097:blood; D004804:Eosinophils / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood* / Q000276:immunology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology
D047209:Eosinophil Peroxidase; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human