Stimulation of oxidative metabolism in murine polymorphonuclear leukocytes by unopsonized fungal cells: evidence for a mannose-specific mechanism.
Murine polymorphonuclear leukocytes (PMN) are stimulated to produce hydrogen peroxide (H2O2) by some unopsonized fungi, including Coccidioides immitis spherules, Candida albicans blastospores, and Saccharomyces sp. blastospores (zymosan). In this communication we have examined the basis for this stimulation by studying the effects of mannan and its primary constituent, D-mannose, on PMN function in vitro, since this polysaccharide is a significant component in many fungal cell walls. Our results show that mannan stimulated H2O2 production and iodination by PMN and enhanced H2O2 production by cells stimulated with zymosan. Moreover, the amount of H2O2 released by PMN was directly related to the concentration of mannan, and mannan obtained commercially or prepared in our laboratory worked equally well. Mannose, on the other hand, inhibited H2O2 release from PMN stimulated with zymosan or mannan and reduced oxygen consumption, carbon dioxide production, superoxide release, and iodination by these cells as well. With respect to specificity of inhibition, 18 different monosaccharides were examined by using 2 different assays for H2O2 release; and only 2-deoxy-D-glucose, a potent glycolytic inhibitor, reduced H2O2 release from zymosan-stimulated PMN. Furthermore, H2O2 release from cells stimulated with phorbol myristate acetate or opsonized Sephadex was not inhibited by mannose whereas H2O2 release was reduced when PMN were stimulated with C. albicans blastospores or C. immitis spherules in the presence of this sugar. From these data we propose that initiation of PMN oxidative metabolic burst in response to some unopsonized fungi occurs through a mannose-specific mechanism.
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D005260:Female; D005658:Fungi / Q000276:immunology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000378:metabolism*; D009895:Opsonin Proteins; D013172:Spores, Fungal / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology
D008351:Mannans; D009895:Opsonin Proteins; D015054:Zymosan; D006861:Hydrogen Peroxide; D008358:Mannose