DEXTRAN SULFATE ENHANCEMENT OF LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY MURINE PERITONEAL-MACROPHAGES - CORRELATION WITH MACROPHAGE BLOCKADE

Proteose peptone-induced murine peritoneal macrophages (Mphi) were pre incubated with 100-800 mug/ml of dextran sulphate (DS) 500 (M(r) 500 0 00) or DS1000 (M(r) 1000 000). After 2-24 h of the preincubation, the Mphi were stimulated with 1 mug/nil of lipopolysaccharide (LPS) in vit ro for 18 h in DS-free culture medium. The culture supernatants were t hen collected for TNF assay. The LPS-induced TNF activity of Mphi supe rnatant preincubated with DS500 or DS1000 for 6 h was enhanced by up t o about ten-fold compared with those preincubated without DS. This enh ancing effect was not observed when Mphi were preincubated with 100-80 0 mug/ml of low molecular weight DS5 (M(r) 5000) or neutral dextran (D ex) 500 (M(r) 500 000). The enhancement of LPS-induced TNF-alpha produ ction from Mphi was observed after 2 or 4 h of incubation with DS1000 or DS500, respectively. The phagocytic activity of Mphi was determined in vitro by the ingestion index and phagocytic capacity using Sacchar omyces cerevisiae. Treatment with DS500 or DS1000 significantly suppre ssed the phagocytic activity from 2 h after the incubation, but this s uppression was not observed in Mphi incubated with DS5 or Dex500. Our experiments indicate that DS500 and DS1000 act directly on Mphi and en hance LPS-induced TNF-alpha production from Mphi, and that the enhance ment is closely related to the suppression of Mphi phagocytic function .