Immunoglobulin E-mediated Increase in Vascular Permeability Correlates with Eosinophilic Inflammation

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Abstract
An increase in bronchovascular permeability is thought to play an important role in the pathogenesis of allergic asthma. We sought to determine whether the increase in permeability observed 24 h after segmental antigen challenge in ragweed-allergic human volunteers was associated with the infiltration and degranulation of a specific cell type. A 20,000-fold range of antigen concentrations was used to alter the number and type of inflammatory cells recruited to the lung by challenge. Although large numbers of inflammatory cells were recruited to lung air spaces over a large range of antigen concentrations, significant numbers of eosinophils (731.3 +/- 232.9 x 10(3)/ml) were recruited only when the concentration of antigen used for segmental challenge was > or = 100-fold higher than the concentration needed to produce an 8 to 10 mm wheal 20 min after intradermal skin testing. In addition, large increases in bronchoalveolar lavage (BAL) albumin concentration (636.3 +/- 170.5 micrograms/ml) were observed only in this same group of subjects. The correlation coefficient between the logarithms of the BAL eosinophil concentration and albumin concentration was +0.82 (p < 0.001), and between eosinophil-derived neurotoxin and albumin it was +0.88 (p < 0.001). In a stepwise, multiple regression analysis, eosinophils accounted for 67% of the variance in BAL albumin concentration, whereas no other cell type was a significant predictor of albumin flux into BAL fluid. We conclude that eosinophil recruitment and degranulation are associated with large increases in bronchovascular permeability after segmental antigen challenge in humans.

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