Altered adhesion molecule expression and endothelial cell activation accompany the recruitment of human granulocytes to the lung after segmental antigen challenge.
Mounting evidence suggests that inflammatory cells recruited to the lung can contribute to the pathogenesis of asthma. The factors governing the activation and recruitment of circulating cells to the lung remain unknown, but an early step in this process is the interaction of adhesion molecules on circulating cells with those on endothelial cells. We used a segmental antigen challenge model followed 18 h later by bronchoalveolar lavage (BAL) to study granulocyte recruitment to the lung in 14 allergic subjects. Using immunofluorescence and flow cytometry, we determined the expression of the adhesion molecules CD11b, L-selectin (LECAM-1), and VLA-4 on BAL and peripheral blood granulocytes. Total cell count and percentages of recovered eosinophils and basophils were significantly increased in BAL fluids from antigen-challenged segments. Compared with their peripheral blood counterparts, CD11b expression was increased 2- to 3-fold on BAL eosinophils, basophils, and neutrophils (n = 9, P less than 0.05). In contrast, L-selectin expression was significantly decreased on BAL cells (n = 3 to 4, P less than 0.05). Similar phenotypic changes were observed on all three cell types, and on neutrophils recovered from saline-challenged control lung segments. In two subjects, VLA-4 alpha (CD49d) expression on BAL eosinophils was 78 +/- 5% of that seen on peripheral blood eosinophils. Because ELAM-1 (endothelial leukocyte adhesion molecule-1, E-selectin) expression occurs during allergic inflammation and is shed after endothelial activation, we used a sensitive enzyme-linked immunosorbent assay to analyze BAL supernatants for a soluble form of this molecule (sELAM-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Georas
S N
SN
Division of Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
Liu
M C
MC
Newman
W
W
Beall
L D
LD
Stealey
B A
BA
Bochner
B S
BS
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin; D008168:Lung / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D017452:Receptors, IgG; D019041:L-Selectin