Bronchial biopsy evidence for leukocyte infiltration and upregulation 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 (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV1 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.
Montefort
S
S
Department of Immunopharmacology, University Medicine, Southampton General Hospital, United Kingdom.
Gratziou
C
C
Goulding
D
D
Polosa
R
R
Haskard
D O
DO
Howarth
P H
PH
Holgate
S T
ST
Carroll
M P
MP
D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000032:analysis*; D019040:E-Selectin; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D013997:Time Factors; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1
D000485:Allergens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1