ALTERED ADHESION MOLECULE EXPRESSION AND ENDOTHELIAL-CELL ACTIVATION ACCOMPANY THE RECRUITMENT OF HUMAN GRANULOCYTES TO THE LUNG AFTER SEGMENTAL ANTIGEN CHALLENGE

被引:151
作者
GEORAS, SN
LIU, MC
NEWMAN, W
BEALL, LD
STEALEY, BA
BOCHNER, BS
机构
[1] JOHNS HOPKINS UNIV,CTR ASTHMA & ALLERGY,DIV CLIN IMMUNOL,5501 BAYVIEW CIRCLE,BALTIMORE,MD 21218
[2] OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD
[3] JOHNS HOPKINS UNIV,CTR ASTHMA & ALLERGY,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21218
关键词
D O I
10.1165/ajrcmb/7.3.261
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 < 0.05). In contrast, L-selectin expression was significantly decreased on BAL cells (n = 3 to 4, P < 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). sELAM-1 was detected in 10X concentrated BAL fluid only after antigen challenge (1.01 +/- 0.05 versus 0.06 +/- 0.03 ng/ml, antigen versus saline challenge, n = 12, P < 0.05). These data show that altered adhesion molecule expression and endothelial activation accompany cell recruitment to the lung during allergic inflammation. Because similar phenotypic changes were observed on BAL neutrophils recovered after saline challenge, these events appear to be associated with leukocyte recruitment regardless of stimulus. The precise mechanism responsible for the enhanced recruitment of eosinophils and basophils after antigen challenge remains to be elucidated.
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页码:261 / 269
页数:9
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