GLYCOSPHINGOLIPIDS FROM SPHINGOMONAS-PAUCIMOBILIS INDUCE MONOKINE PRODUCTION IN HUMAN MONONUCLEAR-CELLS

Glycosphingolipids (GSL) isolated from the gram-negative lipopolysacch aride (LPS)-free bacterium Sphingomonas paucimobilis have remarkable s tructural similarities with LPS and its hydrophobic part, termed lipid A. Like LPS, but in contrast to the structurally related ceramides an d cerebrosides, GSL contain an or-linked, negatively charged pyranosid ic glycosyl component adjacent to the lipid portion and are capable of forming membranes. Because of these similarities, it was of interest to investigate whether these GSL are also able to induce monokine prod uction in human mononuclear cells (MNC). Our results show that a GSL c ontaining four sugar residues (GSL-4A) induced the release of tumor ne crosis factor, interleukin-6, and interleukin-l in MNC, whereas GSL-1, containing only one glycosyl residue, was inactive. A minimal concent ration of 1 mu g of GSL-4A per mi was necessary to induce monokine pro duction in MNC, whereas LPS was as active at a 10,000-fold-lower conce ntration (0.1 ng/ml). Both GSL-4A-induced monokine production and LPS- induced monokine production were reduced by the bactericidal/permeabil ity-increasing protein and GSL-1. In contrast to LPS, GSL-4A-induced m onokine release could be inhibited neither by an anti-CD14 monoclonal antibody nor by lipid A partial structures. We therefore conclude that at the receptor level, different mechanisms are involved in the LPS- and GSL-4A-induced monokine release.