Fas (CD95, APO-1) antigen expression and function in murine liver endothelial cells: implications for the regulation of apoptosis in liver endothelial cells.

The Fas (CD95, APO-1) receptor is a membrane-associated polypeptide that can mediate apoptosis in various cell types. Although Fas receptor is expressed in endothelial cells (EC), little is known about its function in these cells. The expression of Fas by liver endothelial cells (LEC) suggests that upon stimulation, apoptosis may occur in these cells. We show that Fas is highly and constitutively expressed in cloned murine liver endothelial cells (LEC-1). In contrast, FasL expression was not detected at the protein and mRNA level in these cells. Our results show that Fas ligation in LEC-1 induces apoptotic cell death, indicating that Fas receptor is functional in these cells. The doses of Fas agonist required to induce LEC-1 apoptosis were higher than those used previously in other cells, including hepatocytes, suggesting that LEC-1 are highly resistant to the Fas apoptotic pathway. TNF treatment of LEC-1 induced up-regulation of Fas receptor on these cells. In contrast, TNF did not induce the expression of FasL on LEC-1. An increased susceptibility to Fas-mediated apoptosis was observed in TNF-treated LEC-1. Enhanced susceptibility to Fas-mediated apoptosis was also observed in LEC-1 pretreated with actinomycin D, suggesting that transcription of message coding for protective proteins is necessary to protect these cells against Fas-mediated apoptosis. Up-regulation of VCAM-1 and ICAM-1 was observed in LEC-1 treated with a dose of Fas agonist that does not induce apoptosis. To our knowledge, this is the first report that Fas mediates apoptosis in LEC, suggesting that apoptosis of these cells may participate in the liver damage observed in animals after receiving anti-Fas mAb or soluble FasL. Our findings also suggest that the Fas/FasL system may transduce activating signals independently of cell death in LEC-1.

Autoantibodies to phospholipids and nuclear antigens in non-pregnant and pregnant Colombian women with recurrent spontaneous abortions.

Autoantibodies to negatively charged phospholipids have been reported to be associated with thrombotic events, thrombocytopenia and adverse pregnancy outcome, such as intrauterine growth retardation and recurrent spontaneous abortions (RSAs). In this study, autoantibodies to 6 phospholipid antigens and antinuclear antibody (ANA) were tested in Colombian women with a history of RSAs. Sixty-eight non-pregnant and 25 pregnant women with a history of RSAs comprised the study group. Twenty-five non-pregnant normal healthy women and thirty-one normal pregnant women served as controls. The non-pregnant women with RSAs showed a higher incidence of autoantibodies to cardiolipin (23% positive) as compared with non-pregnant normal controls (0% positive; P < 0.005). The incidence of autoantibodies to cardiolipin (28%; P < 0.005), phosphatidylethanolamine (16%; P < 0.005), phosphatidylserine (16%; P < 0.05), phosphatidylglycerol (16%; P < 0.05), phosphatidic acid (16%; P < 0.01) and phosphatidylinositol (20%; P < 0.01), in the pregnant women with RSAs was significantly higher than that of normal pregnant controls. There was no difference in the incidence of ANA in either group. In conclusion, women with a history of RSAs have a higher incidence of autoantibodies to phospholipids when compared to pregnant and non-pregnant normal controls. Autoimmune serological work-up is indicated during pregnancy in women with a history of RSAs.