Granuloma formation in mice by liposomes of new glycolipid containing mycolic acids, "trehalose 2,3,6'-trimycolate"

Abstract

After intravenous administration of liposomes containing a novel glycolipid, trehalose 2,3,6'-trimycolate, isolated from Rhodococcus aurantiacus, the granuloma formation was observed distinctively in the lungs, spleen and liver of ICR mice. The concentration of the glycolipid in liposomes influenced profoundly on the inducibility for granulomas and the liposomes containing 10 mol% of trehalose 2,3,6'-trimycolate showed the highest activity for the granuloma formation in mice without a significant loss of body weight of mice with a less toxicity. EggPC liposomes are of more highly inducible for the granuloma formation in mice than eggPC:PS (7:3, mol ratio) liposomes or eggPC:Chol (9:1, mol ratio) liposomes, suggesting that cholesterol in liposomes was not necessarily essential for inducing granulomas in mice. Among the various PC liposomes, synthetic dimyristoyl-phosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC) liposomes were of highly inducible, although a high responsiveness was also observed with natural lecithines such as egg or soy PC. However, distearoylphosphatidylcholine (DSPC) liposomes did not show any activity for the granuloma formation in any organs of mice. Organ responsiveness differed significantly in the micelle forms injected. Glycolipid entrapped with eggPC-Chol liposomes showed a lower lung index below 1.0, in contrast to w/o/w micelles containing Freunds' incomplete adjuvant, which showed a higher granuloma formation in the lungs. It was also noted that the toxicity of glycolipid containing liposomes was comparatively lower than the toxicity of glycolipid containing w/o/w micelles, indicating that the liposomes appeared to be more suitable for the induction of the immunomodifying activities of mycolic acid-containing glycolipids than w/o/w micelles.