RELATIONSHIP BETWEEN INDUCTION OF MACROPHAGE CHEMOTACTIC FACTORS AND FORMATION OF GRANULOMAS CAUSED BY MYCOLOYL GLYCOLIPIDS FROM RHODOCOCCUS-RUBER (NOCARDIA-RUBRA)

Mycoloyl glycolipids cause granulomas in the lungs, liver, and spleen of mice, but the mechanism is not fully understood, To understand the role of macrophage chemotactic factors (MCFs) in granuloma formation, we prepared various mycoloyl glycolipids with different carbohydrate m oieties: trehalose dimycolate (TDM), glucose mycolate (GM), mannose my colate (MM), and fructose mycolate (FM) from Rhodococcus ruber, and ex amined the relationship between their MCF induction in peritoneal macr ophages and the extent of granuloma formation, The molecular mass of e ach glycolipid was confirmed by fast-atom-bombardment mass-spectrometr y, TDM or GM caused granulomas in the lungs, spleen, and liver of ICR mice, but MM and FM did not, The culture supernatant of peritoneal mac rophages stimulated with TDM or GM increased macrophage migration, whe reas MM and FM had no chemotactic activity, The activity of interleuki n-1 (IL-1) in the supernatant was increased equally by each glycolipid and was therefore not related to chemotaxis. Tumor necrosis factor-al pha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor ( GM-CSF) were not detected in the four supernatants, The TDM-induced MC F was heat-stable, trypsin-labile, and undialyzable. Furthermore, we s eparated two MCP active fractions from the supernatant of TDM-stimulat ed macrophages by gel filtration, These factors acted on macrophages b ut not on neutrophils, Our results suggested that macrophages recogniz e the sugar moieties of mycoloyl glycolipids and may, in response, gen erate a MCF that may play an important role in the macrophage or monoc yte recruitment which is essential prior to granuloma formation.