Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils.

BACKGROUND: Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of inflammatory airway diseases, including asthma, rhinitis, and polyposis. However, little is known about the mechanisms involved in the deposition of these tissue-damaging granular products in vivo. OBJECTIVE: We sought to determine the occurrence of degranulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to identify the frequency of apoptotic eosinophils in inflamed upper airway tissue. METHODS: Eosinophil-rich nasal polyps were processed for transmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue staining for eosinophil peroxidase. RESULTS: The mean proportion of eosinophil subtypes were intact and resting (6.8%), intact but degranulating (83%), cytolytic or Cfegs (9.9%), and apoptotic (0.0%). All degranulating eosinophils exhibited piecemeal degranulation. The occurrence of Cfegs was confirmed in nonsectioned whole-mount preparations. Depending on the appearance of their core and matrix, the specific granules were divided into four subtypes, and a degranulation index (altered per total granules) was calculated for each eosinophil. Cytolytic eosinophils had a much lower degranulation index than intact eosinophils present in the same tissue (P < .001). CONCLUSIONS: These data indicate that eosinophil cytolysis is present in human airway mucosa, that its occurrence is not an artifact of the means of tissue handling, and that cytolysis of eosinophils may occur without prior extensive degranulation. We suggest that eosinophil cytolysis is a major activation mechanism, which occurs along with, but is distinct from, other types of degranulation.

Contractile effects of histamine in large and small respiratory airways.

The described technique allows recording of circular smooth muscle activity in isolated airways approx. 1 mm in diameter (bronchioles). It also allows recording of graded contractile and relaxant responses to drugs. Bronchiolar preparations and spirally cut airways (diameters 3-6 mm) were obtained from cat, dog, guinea-pig and man. Histamine is shown to contract cat bronchioles, large airways in cat being unaffected. The contraction is blocked by brompheniramine, but not by atropine. Other contractile agents, cholinoceptor-stimulants, prostaglandin F2alpha'5-hydroxy-tryptamine, and potassium contract the isolated cat airways irrespective of their size. In preparations from dog, guinea-pig and man,histamine was shown to contract both small and large respiratory airways. The effect was blocked by brompheniramine, which did not change the effect of acetylcholine or pilocarpine. Both large and small airways contracted to cholinoceptor stimulation Within species, small and large airways were similarly sensitive to the contractile agents, except for histamine in cat airways. The present findings show a size-and species dependent effect of histamine in respiratory airways. The effect of histamine in isolated cat airways might partly explain the pulmonary effect of histamine in vivo. The importance of including both small and large airways in studies of contractile and relaxant effects is emphasized.