FIBRONECTIN AND ITS ALPHA(5)BETA(1)-INTEGRIN RECEPTOR ARE INVOLVED INTHE WOUND-REPAIR PROCESS OF AIRWAY EPITHELIUM

The cell migration that occurs during wound repair is dependent on mod ifications of the cell-matrix interaction in which extracellular matri x proteins and their receptors, the integrins, are involved. To study the interactions between airway epithelial cells and the extracellular matrix during the process of wound repair, we developed an in vitro w ound model of human epithelial cells. Surface epithelial cells were di ssociated from human nasal polyps and cultured on a type I collagen ma trix. At confluency, a wound was made by the addition of 2 mu l of NaO H (1 N) to the cell culture. After the cell culture was washed, the wo und area was recorded every 12 h for 96 h by; a videomicroscopic techn ique. We calculated the wound-repair index that represents the decreas e in the wound area per hour. Using immunofluorescence techniques, we first examined the localization, during wound repair, of fibronectin a nd of the beta(1), alpha(v)-, alpha(2)-, alpha(3)-, and alpha(6)-integ rin subunits. Secondly, we carried out a series of wound-repair blocki ng experiments with the use of anti-integrin or anti-fibronectin antib odies diluted in the culture medium. We observed that fibronectin and the alpha(5)-integrin subunit were exclusively expressed by the migrat ory cells in the wounded area. No difference in the localization of th e alpha(2)-, alpha(3)-, and alpha(6)-integrin subunits was observed be tween the nonrepairing and repairing cells. The blocking experiments s howed a significant decrease in the wound-repair index in the presence of either the anti-beta(1), -alpha(3), -alpha(5), or the anti-fibrone ctin antibodies. Furthermore, the addition of fibronectin to the cultu re medium induced a significant increase in the wound repair index. Th ese results suggest that fibronectin and the corresponding alpha(5) be ta(1)-integrin play an important role in the process of airway epithel ium wound repair.