The repair of the bronchiolar epithelium damaged by cell-mediated, physical, or chemical insult requires epithelial cell migration over a provisional matrix composed of complexes of extracellular matrix molecules, including fibronectin and laminin. These matrix molecules support migration and enhance cell adhesion. When cells adhere too tightly to their matrix they fail to move; but if they adhere too little, they are unable to develop the traction force necessary for motility. Thus, we investigated the relative contributions of laminin and fibronectin to bronchiolar cell adhesion and migration using the immortalized bronchial lung epithelial cell line (BEP2D) and normal human bronchial epithelial (NHBE) cells, both of which assemble a laminin a3b3g2 (LM332)/fibronectin-rich matrix. Intriguingly, BEP2D and NHBE cells migrate significantly faster on an LM332-rich matrix than on fibronectin. Moreover, addition of fibronectin to LM332 matrix suppresses motility of both cell types. Finally, fibronectin enhances the adhesion of both BEP2D and NHBE cells to LM332-coated surfaces. These results suggest that fibronectin fine tunes LM332-mediated migration by boosting bronchiolar cell adhesion to substrate. We suggest that, during epithelial wound healing of the injured airway, fibronectin plays an important adhesive role for laminin-driven epithelial cell motility by promoting a stable cellular interaction with the provisional matrix.
Keywords: motility; adhesion; extracellular matrixThe epithelial cell sheet lining the bronchial airway is a selective barrier that allows the passage of solutes and ions, but prevents pathogens or pollutants moving from the epithelial lumen into the connective tissue. Prolonged exposure to cigarette smoke, inhaled irritants, or respiratory allergens damages the epithelial cells lining the bronchial airway and compromises the barrier function of the epithelium. Activation of the immune system can worsen epithelial damage. As a result, many chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease, are characterized by basement membrane thickening, epithelial cell shedding, and a loss of epithelial barrier integrity (1, 2). Repair of the damaged airway epithelium requires the migration of undamaged epithelial cells or epithelial progenitor cells to the sites of airway injury.Wound healing in the bronchial epithelium is a multistep process involving the detachment of unwounded epithelial cells from their matrix, rearrangement of their cytoskeletons, development of traction forces necessary for directed migration over the wound, establishment of new interactions with the wound surface via the binding of receptors to matrix proteins covering the wound bed, and the orchestration of assembly of a new basement membrane (3, 4). The focus of the current study was to gain new insight into the role that extracellular matrix proteins and matrix receptors play in regulating the migration of bronchial epithelial cells. In this regard, bronchial epithelial cells neighboring...