Regulation of tissue-type plasminogen activator and Its Inhibitor (PAI-1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line

The plasminogen activator (PA) system is thought to play a major role in th e proteolytic events associated with spermatogenesis. The mechanisms contro lling the expression of PA and of its major physiological inhibitor, plasmi nogen activator inhibitor type-1 (PAI-1), in the seminiferous epithelium ar e still unknown. In the present study we analyzed the expression of PA and PAI-1 in a murine Sertoli cell line (42GPA9) in response to stimulation by lipopolysaccharides (LPS) used to activate the phagocytic activity of these cells. Immortalized Sertoli cells cultured under basal conditions secreted predominantly tissue-type PA (tPA) as demonstrated by zymographic analysis and the presence of tPA transcripts. In zymographic experiments a larger m olecular weight proteolytic band corresponding to the formation of PA-PAI-1 complex was also observed. The stimulation of immortalized Sertoli cells b y LPS resulted in both alteration of the apparent tPA molecular weight to a higher form and transient increase in PAI-1 biosynthesis. The phorbol este r TPA stimulates similarly PAI-1 synthesis in the Sertoli cell line, while 8-bromo-cAMP has no effect. These results suggest for the first time the ex istence of a direct linkage between molecular events triggered by phagocyto sis and regulation of tPA and PAI-1 in Sertoli cells. (C) 1999 Academic Pre ss.