Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation.
Eosinophil degranulation is a characteristic feature of asthma and allergic rhinitis. However, degranulated eosinophils have not been convincingly demonstrated in the common mouse models of these airway diseases. This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also examined mouse and human blood eosinophils after in vitro incubation with formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure induced significant nasal and lung eosinophilia, we did not observe any of the known cellular processes by which eosinophils release their granule products, i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The occurrence of other allergen-induced degranulation events was ruled out because no difference in granule morphology was observed between lung-tissue eosinophils and blood or bone-marrow eosinophils from control animals. Accordingly, there was no detectable extracellular EPO in lung tissues of allergic mice. Similarly, mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP and PMA, whereas the same treatment of human eosinophils resulted in extensive degranulation. This investigation indicates that OVA-induced airway inflammation in the present mouse strains does not involve significant eosinophil degranulation. It is speculated that this dissimilarity from the human disease may be due to a fundamental difference in the regulation of mouse and human eosinophils.
Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden. monika.malm-erjefalt@klinfarm.lu.se
M
M
Malm-Erjefält
C G
CG
Persson
J S
JS
Erjefält
D000818:Animals; D015550:Cell Degranulation / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005089:Exocytosis; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009300:Nasal Septum; D010047:Ovalbumin; D010544:Peroxidases / Q000032:analysis; D020545:Respiratory Mucosa / Q000502:physiology / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009240:N-Formylmethionine Leucyl-Phenylalanine; D010047:Ovalbumin; D010544:Peroxidases; D013755:Tetradecanoylphorbol Acetate