Activation of human neutrophils by mycobacterial phenolic glycolipids

The interaction between mycobacterial phenolic glycolipids (PGLs) and phago cytes was studied. Human neutrophils were allowed to interact with each of four purified mycobacterial PGLs and the neutrophil production of reactive oxygen metabolites was followed kinetically by luminol-/isoluminol-amplifie d chemiluminescence. The PGLs from Mycobacterium tuberculosis and Mycobacte rium kansasii, respectively, were shown to stimulate the production of oxyg en metabolites, while PGLs from Mycobacterium marinum and Mycobacterium bov is BCC, respectively, were unable to induce an oxidative response. Periodat e treatment of the M. tuberculosis PGL decreased the production of oxygen r adicals, showing the importance of the PGL carbohydrate moiety for the inte raction. The activation, however, could not be inhibited by rhamnose or fuc ose, indicating a complex interaction which probably involves more than one saccharide unit. This is in line with the fact that the activating PGLs fr om M. tuberculosis and M. kansasii contain tri- and tetrasaccharides, respe ctively, while the nonactivating PGLs from M. marinum and M. bovis BCG each contain a monosaccharide. The complement receptor 3 (CR3) has earlier been shown to be of importance for the phagocyte binding of mycobacteria, but d id not appear to be involved in the activation of neutrophils by PGLs. The subcellular localization of the reactive oxygen metabolites formed was rela ted to the way in which the glycolipids were presented to the cells.