Prostaglandin E2 depresses antigen-presenting cell function of peritoneal macrophages.

Abstract Eicosanoids play a prominent role in trauma. Such mediators of inflammation negatively influence cell-mediated immunity (CMI). There is, however, no information available on the effect of eicosanoids on a critical event in CMI, i.e., antigen-presenting (AP) cell function of macrophages (Mφ), a cellular process responsible for the activation of T and B lymphocytes. The aim of this study, therefore, was to examine the effect of prostaglandin E 2 (PGE 2 ) and thromboxane B 2 (TXB 2 ) on AP cell function of the peritoneal Mφ. To study this, a T-helper-cell clone, D10.G4.1 was employed. This cell clone proliferates in the presence of Ia k (Class II glycoprotein, MAC product) bearing Mφ and specific antigen (conalbumin A) thus directly reflecting the AP capability of the Mφ. Peritoneal Mφ were harvested from B10.BR mice (H2 k ) and their AP was tested in vitro by incubating varying numbers of Mφ with 2 × 10 4 D10.G4.1 cells/well and conalbumin (400 μg/ml) in the presence and absence of different concentrations of PGE 2 or TXB 2 . Cultures were incubated for 72 hr, pulsed with [ 3 H]-thymidine, and harvested. At concentrations of 10, 30, and 100 n M of PGE 2 , D10.G4.1 proliferations were 38, 35, and 20% of control, respectively ( P 2 added at the above-mentioned concentrations did not suppress the proliferative response of D10. Thus, PGE 2 but not TXB 2 has a potent immunosuppressive effect on AP of peritoneal Mφ. The above results lead us to conclude that the elevated levels of PGE 2 in hemorrhage and trauma could be responsible for perturbations in CMI via depression of AP cell function of the Mφ. In addition, this defective AP process might further increase the susceptibility to sepsis and multiple organ failure following trauma.