EFFECTS OF PROSTAGLANDIN-E2 AND CYCLIC-AMP ON UPTAKE OF IMMUNOGLOBULIN-G COMPLEXES BY CULTURED MACROPHAGES

The uptake of immune complexes by macrophages (MP) may be important in disease states in which circulating immune complexes are increased. We undertook the present study to determine the effects of prostaglandin E2 (PGE2) and adenosine 3',5'-cyclic monophosphate (cAMP) on the uptake of immunoglobulin G complexes (IgG complexes) by MP. The uptake of I-125-IgG-gold particles (IgG-gold) was measured in the established MP cell line J774.16 following pretreatment with PGE2, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), PGE2 plus IBMX, the cyclooxygenase inhibitor indomethacin (IM), and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). Preincubation with PGE2 at concentrations from (10(-12)) to (10(-5)M) revealed significantly diminished uptake of IgG-gold at (10(-6)) and (10(-5)M) (in counts per min per well, PGE2 [10(-6)M], 5,401 +/- 140; control, 17,150 +/- 493, p < 0.00 1); (PGE2 [10(-5) M], 3,835 +/- 172; control, 17,150 +/- 493, p < 0.001). IBMX (10(-3) M) alone did not significantly alter IgG-gold uptake (IBMX, 14,450 +/- 1938; control, 14,840 +/- 995, p < 1.0). PGE2 (10(-6) M) plus IBMX (10(-3) M) significantly suppressed IgG-gold uptake (in counts per min per well, PGE2 PIUS IBMX, 3,659 +/- 129; control 18,296 +/- 486, p < 0.001). PGE2 (10(-6) M) alone also suppressed IgG-gold uptake versus control (PGE2, 4,578 +/- 105; control, 18,296 +/- 486, p<0.001). PGE2 (10(-6) M) plus IBMX (10(-3) M) caused greater suppression of IgG-gold uptake compared to PGE2 (10(-6) M) alone (PGE2 plus IBMX, 3,659 +/- 129; PGE2 alone, 4,578 +/- 105, p < 0.001). IM (10(-6) M) caused a significant increase in IgG-gold uptake (IM, 16,590 +/- 639; control, 13,080 +/- 860, p < 0.02). DBcAMP (10(-4) M) was found to significantly diminish uptake of IgG-gold (DBcAMP, 8,736 +/- 784; control, 15,370 +/- 1066, p < 0.0 1). This data suggests that PGE2 may play an important role in modulating disorders characterized by elevated levels of circulating immune complexes by reducing uptake of these substances by MP. This effect of PGE2 appears to be mediated via generation of cAMP.