TRANSMIGRATION OF HUMAN NEUTROPHILS ACROSS AIRWAY EPITHELIAL-CELL MONOLAYERS IS PREFERENTIALLY IN THE PHYSIOLOGICAL BASOLATERAL-TO-APICAL DIRECTION

To study the mechanisms involved in the movement of neutrophils from t he blood stream into the lung airways, we investigated human neutrophi l transmigration across a monolayer of human airway epithelial cells, both in the apical-to-basolateral direction and in the more physiologi c basolateral-to-apical direction. Migration of human neutrophils acro ss monolayers of human airway epithelial H292 cell-line cells and prim ary bronchial epithelial cells occured most efficiently in the basolat eral-to-apical direction, both after the addition of chemoattractants to resting epithelial cells and across interleukin-1 beta (IL-1 beta)- stimulated epithelial cells. Blocking studies with monoclonal antibodi es revealed that the migration of neutrophils was mediated by the CR3 adhesion molecule (CD11b/CD18) on the neutrophils. IL-1 beta-treated e pithelial cells caused neutrophil movement via the secretion of chemoa ttractants. The most potent chemoattractant released by the epithelial cells was found to be IL-8, because the IL-1 beta-induced migration w as inhibited for 75 +/- 10% by the addition of an antibody against IL- 8. After apical stimulation of the epithelial cells with an optimal co ncentration ofIL-1 beta, 27 +/- 4 ng/ml IL-8 was found in the supernat ant at the apical side of epithelial cells. Platelet-activating factor (PAF) synthesis by the epithelial cells did not play a role in neutro phil transmigration, as was demonstrated by the lack of inhibition of this process after addition of the PAF-receptor antagonist WEB 2086. W e conclude that the movement of neutrophils across airway epithelial c ell monolayers occurs preferentially in the physiologic basolateral-to -apical direction, indicating that the polarity of epithelial cells is important for neutrophil transmigration.