Induction of fibroblast apoptosis by anti-CD44 antibody: implications for the treatment of fibroproliferative lung disease.
Fibroblast migration and proliferation within the alveolar wall and airspace after lung injury can lead to the development of fibrosis. Fibroblast cell surface CD44 is an adhesion receptor for provisional matrix proteins and mediates fibroblast invasion into fibrin matrices. Here we show that incubation of cultured fibroblasts with an anti-CD44 monoclonal antibody induces fibroblast detachment from the substratum and morphological changes compatible with apoptosis. In addition, we show that anti-CD44 monoclonal antibody rapidly induces fibroblast apoptosis within fibrin matrices. The effect of anti-CD44 antibody on induction of fibroblast apoptosis occurred within 8 hours and was dose dependent. Anti-CD44 antibody also induced fibroblast apoptosis in suspension. Furthermore, fibroblasts plated on anti-CD44-antibody-coated surfaces initially attached and spread on the antibody; however, after an 8-hour incubation time, many of the cells developed characteristic morphological features of apoptosis. Collectively, these data indicate that apoptosis did not result solely due to detachment from the substratum. Our results identify a new function for fibroblast cell surface CD44 related to the control of cell viability. We suggest this function may be important in fibroblast population control and could potentially be exploited in designing anti-fibrotic therapies.
Henke
C
C
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Bitterman
P
P
Roongta
U
U
Ingbar
D
D
Polunovsky
V
V
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology*; D005355:Fibrosis / Q000473:pathology / Q000628:therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology* / Q000628:therapy*
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors