BRONCHIAL BIOPSY EVIDENCE FOR LEUKOCYTE INFILTRATION AND UP-REGULATION OF LEUKOCYTE-ENDOTHELIAL CELL-ADHESION MOLECULES 6 HOURS AFTER LOCAL ALLERGEN CHALLENGE OF SENSITIZED ASTHMATIC AIRWAYS

We have examined the mucosal changes occurring in bronchial biopsies from six atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared them with biopsies from saline-challenged segments from the same subjects at the same time point. All the subjects developed localized bronchoconstriction in the allergen-challenged segment and had a decrease in forced expiratory volume in 1 s (FEV(1)) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV(1) from baseline by 20% (P < 0.05) 24 h postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03), eosinophils (P = 0.025), mast cells (P = 0.03), and CD3(+) lymphocytes (P = 0.025), but not in CD4(+) or CD8(+) lymphocyte counts. We also detected an increase in endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P < 0.005), but not vascular cell adhesion molecule type 1 expression with a correlative increase in submucosal and epithelial LFA(+) leucocytes (P < 0.01). Thus, in sensitized asthmatics, local endobronchial allergen instillation leads to an increased inflammatory cell infiltrate of the airway mucosa that involves upregulation of specific adhesion molecules expressed on the microvasculature.