A study on the mechanism of activation of peritoneal exudate macrophages from MRL/MpJ-lpr/lpr mice

MRL/MpJ-lpr/lpr (lpr/lpr) mice are congenic mice of the lpr gene which encodes the massive proliferation of unusual T cells characteristic of Thy 1+, Lyl1+, L3T4-, Lyt2- and B220+ on cell surface. These mice spontaneously develop a progressive autoimmune disease such as glomerulonephritis, arthritis and granulomatous arteritis. Until now, it has been reported that peritoneal exudate macrophages (PEM) from lpr/lpr mice are activated in comparison with those from MRL/MpJ-+/+ (+/+) mice. In this paper, five PEM functions [anti-tumor activity, IL-1 activity, TNF activity, superoxide (O2-) production and proliferative capacity] were analysed to elucidate the mechanism of activation of PEM from lpr/lpr mice. The results indicated that lpr/lpr PEM had a significant increase in cytostasis and O2- production and a significant decrease in proliferative capacity, suggesting that PEM from lpr/lpr mice were activated to the level of primed macrophage. To examine the effect of contaminated nonadherent peritoneal exudate cells (NAPEC) from lpr/lpr mice on PEM activity, cell mixing experiments were performed. B220- cells out of NAPEC from lpr/lpr mice significantly enhanced O2- production by +/+ PEM. Furthermore, Lyt2+ splenic T cells also enhanced O2- production by +/+ PEM. The culture supernatants of spleen cells from lpr/lpr mice contained so called "MAF" activity, because they enhanced O2- production by +/+ PEM significantly. Moreover, the culture supernatants of Con A-stimulated spleen cells from lpr/lpr mice showed higher IFN-gamma activity than those from +/+ mice. Such higher IFN-gamma activity was present in the supernatants of Con A-stimulated B220- splenic T cells. These results suggested that Lyt2+ NAPEC from lpr/lpr mice produced MAF-like-lymphokine, possibly IFN-gamma, which activated PEM in vivo. While the culture supernatants of non-stimulated PEM from MRL mice had no IL-1 and TNF activity, those of recombinant IFN-gamma-stimulated PEM from lpr/lpr mice had higher IL-1 and TNE activity than those from +/+ mice. These data indicated that lpr/lpr PEM were more sensitive to IFN-gamma than +/+ PEM.