V. Godding et al., ADHESION OF ACTIVATED EOSINOPHILS TO RESPIRATORY EPITHELIAL-CELLS IS ENHANCED BY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA, American journal of respiratory cell and molecular biology, 13(5), 1995, pp. 555-562
Eosinophilic infiltration and damage to airway epithelium are characte
ristic features of asthma. To assess possible interactions between eos
inophils and airway epithelium, Percoll-purified human peripheral bloo
d eosinophils were evaluated for their ability to adhere to respirator
y epithelial cell (REC) cultures. REC (an immortalized cell line, A549
, and primary bronchial epithelial cells) were grown in 96-well tissue
culture plates, treated with proinflammatory cytokines (TNF-alpha or
IL-1 beta), and eosinophil adhesion to these tissues was determined. C
ytokine treatment of the REC cultures significantly increased expressi
on of intercellular adhesion molecule-1 (ICAM-1) (P < 0.01). Eosinophi
ls demonstrated a variable baseline adhesion to untreated REC which wa
s then significantly increased following activation with phorbol myris
tate acetate (PMA) (P < 0.01). Furthermore, treatment of REC monolayer
s with TNF-alpha or IL-1 beta significantly increased adhesion of PMA-
stimulated eosinophils (P < 0.01). To delineate the adhesion proteins
involved in the cell-cell interactions, assays were performed in the p
resence of specific blocking monoclonal antibodies to eosinophil CD18,
CD11a, or CD11b, and REC ICAM-1 molecules. Blocking antibodies to ICA
M-1 had no significant effect on levels of eosinophil adhesion. In con
trast, antibodies to CD18, CD11a, and CD11b significantly decreased (P
< 0.01) eosinophil adhesion, thus demonstrating pivotal roles for the
CD11/CD18 (Pt) integrins, but not necessarily for ICAM-1, in interact
ions between the REC and eosinophils. These data demonstrate that TNF-
alpha and IL-1 beta increase eosinophil adhesion to human respiratory
epithelial cell cultures by induction of ligands recognized by eosinop
hil beta(2) integrins.