EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR RECEPTOR IS INCREASED FOLLOWING BLEOMYCIN-INDUCED LUNG INJURY INRATS

To investigate the potential role of transforming growth factor-cy (TG F-cr) and the epidermal growth factor receptor (EGF-R) in the fibropro liferative response to acute lung injury, we determined lung steady-st ate TGF-alpha and EGF-R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-cu and EGFR immunoreactive protein of bleomycin-i njured and control rat lungs. At 2 and 4 days after a single intratrac heal injection of bleomycin, TGF-alpha mRNA levels increased to 159% a nd 184% of control values, respectively. EGF-R mRNA levels increased t o 163%, 314%, and 170% of control values at 1, 7, and 14 days after bl eomycin instillation. TGF-alpha protein levels in whole lung extracts increased to 230% of control values at 4 days after bleomycin administ ration. TGF-alpha and EGF-R immunoreactivity was detected in macrophag es, alveolar septal cells, and airway epithelium of control and bleomy cin-injured animals with an apparent increase in the intensity and num ber of specifically immunostained cells following lung injury. TGF-alp ha and EGF-R immunoreactive proteins were detected in foci of cellular proliferation and in areas of intraalveolar fibrosis. We conclude tha t TGF-alpha and the EGF-R are present in normal and bleomycin-injured rat lung and that the expression of this growth factor and its recepto r are up-regulated following lung injury. These results suggest that i ncreased expression of TGF-alpha and the EGFR may be an important mech anism that modulates the fibroproliferative response to acute lung inj ury.