KL-6, A HUMAN MUC1 MUCIN, IS CHEMOTACTIC FOR HUMAN FIBROBLASTS

KL-6 in serum and bronchoalveolar lavage fluid has been reported to be a sensitive marker indicating the activity of fibrosing lung diseases . The molecule is clustered in MUC1 mucin according to the findings of immunohistochemical and cytometric studies. To elucidate the pathogen ic role of KL-6 in fibrosing lung disease, we characterized its bioche mical properties and examined whether purified KL-6 is chemotactic for human fibroblasts in vitro using modified Boyden chambers. Biochemica l properties of purified KL-6 were similar to those of other MUC1 muci ns previously reported. KL-6 promoted the migration of 5 of 5 human lu ng fibroblasts and 3 of 4 human skin fibroblasts. Checkerboard analysi s revealed that KL-6 was chemotactic as well as chemokinetic. Though p latelet-derived growth factor, fibroblast growth factor, or fibronecti n were also chemotactic for fibroblasts in the experimental system, on ly fibronectin augmented KL-6-induced chemotaxis. These observations i ndicate that KL-6 is one of the chemotactic factors for most fibroblas ts and that the increased KL-6 in the epithelial lining fluid in small airways may cause the intra-alveolar fibrosis in fibrosing lung disea ses.