Prostaglandin E and Thromboxane B2 Release by PMA-Induced U937 Cells in Response to C3b

The human monocytic cell lines HL-60 and U937 were examined for their ability to release PGE and TxB2 in response to the C3 cleavage fragment C3b. It was found that U937 responds to C3b by releasing both eicosanoids only after a 48 h induction period in the presence of PMA. HL-60 failed to respond. The response of U937 was further studied and characterized. It was found that the continual presence of PMA in culture was not required for the response to C3b, and that by replenishing the culture medium every 48 hr, the response could be maintained for up to 12 days. This contrasts with the previously observed behavior of human monocytes, which fail to respond after 24 hr in culture. Further studies demonstrated that maximal levels of PGE and TxB2 were elicited by 25-50 micrograms/ml of C3b, and that the kinetics of appearance of these eicosanoids in culture supernatants was very similar to that previously observed for monocytes. Maximal levels of PGE and TxB2 occurred following 24-48 hr in culture. In addition, a monoclonal a-CR1 antibody stimulated PG release by these cells. It is expected that this cell line will provide a model for study of the influence of cell differentiation on the response of human mononuclear phagocytes to C3b.