Dextran sulphate enhancement of lipopolysaccharide-induced tumour necrosis factor-alpha production by murine peritoneal macrophages: correlation with macrophage blockade.

Proteose peptone-induced murine peritoneal macrophages (M phi) were preincubated with 100-800 micrograms/ml of dextran sulphate (DS) 500 (M(r) 500,000) or DS1000 (M(r) 1,000,000). After 2-24 h of the preincubation, the M phi were stimulated with 1 microgram/ml 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 M phi 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 M phi were preincubated with 100-800 micrograms/ml of low molecular weight DS5 (M(r) 5,000) or neutral dextran (Dex) 500 (M(r) 500,000). The enhancement of LPS-induced TNF-alpha production from M phi was observed after 2 or 4 h of incubation with DS1000 or DS500, respectively. The phagocytic activity of M phi 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 M phi incubated with DS5 or Dex500. Our experiments indicate that DS500 and DS1000 act directly on M phi and enhance LPS-induced TNF-alpha production from M phi, and that the enhancement is closely related to the suppression of M phi phagocytic function.