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 preincubated with 100-800 mug/ml of dextran sulphate (DS) 500 (M(r) 500 000) 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 vitro for 18 h in DS-free culture medium. The culture supernatants were then collected for TNF assay. The LPS-induced TNF activity of Mphi supernatant preincubated with DS500 or DS1000 for 6 h was enhanced by up to about ten-fold compared with those preincubated without DS. This enhancing effect was not observed when Mphi were preincubated with 100-800 mug/ml of low molecular weight DS5 (M(r) 5000) or neutral dextran (Dex) 500 (M(r) 500 000). The enhancement of LPS-induced TNF-alpha production 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 Saccharomyces cerevisiae. Treatment with DS500 or DS1000 significantly suppressed the phagocytic activity from 2 h after the incubation, but this suppression was not observed in Mphi incubated with DS5 or Dex500. Our experiments indicate that DS500 and DS1000 act directly on Mphi and enhance LPS-induced TNF-alpha production from Mphi, and that the enhancement is closely related to the suppression of Mphi phagocytic function.