[Eosinophil and neutrophil degranulation in allergic inflammation: immunohistochemical localization of granule proteins in fatal asthma and stimulus-dependent degranulation in vitro].
Airway inflammation is a central feature of bronchial asthma. The eosinophil, a major infiltrating cell in the airway wall in asthma, expresses its effector function by degranulation of toxic granule proteins. The role of the neutrophil in allergic inflammation is still controversial. In order to clarify the possible involvement of degranulation in allergic inflammation, we studied the immunohistochemical localization of granule proteins of the eosinophil and the neutrophil, namely, major basic protein (MBP) and elastase, respectively, in the lungs from patients with fatal asthma. We found that extracellular deposition of MBP or elastase coexisted with epithelial damage in the airway and that more eosinophils were found in slow onset fatal asthma cases and more neutrophils in sudden onset fatal asthma. These results suggest that inflammatory cell degranulation may have induced tissue injury in cases of fatal asthma, and that there may be two pathologically distinct forms of fatal asthma in terms of involvement of eosinophils or neutrophils. Next we showed that IgA and IgG coupled to Sepharose beads induced eosinophil and neutrophil degranulation. IgA and secretory IgA (sIgA) for neutrophils and sIgA for eosinophils were the most potent stimulators of degranulation. Pretreatment of eosinophils with pertussis toxin (PTX) for 2 h irreversibly abolished sIgA-induced degranulation, whereas PTX treatment only transiently inhibited IgG-induced eosinophil degranulation. Activated PTX catalyzed the in vitro ADP ribosylation of 41- and 44-kDa proteins in eosinophils. A 2-h pretreatment of intact cells with PTX markedly reduced the pools of unmodified 41- and 44-kDa substrates available for subsequent ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fujisawa
T
T
Department of Pediatrics, Mie National Hospital.
Kita
H
H
Sur
S
S
Kobayashi
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001798:Blood Proteins / Q000502:physiology*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D012260:Ribonucleases