A basis for resistance of Blastomyces dermatitidis killing by human neutrophils: inefficient generation of myeloperoxidase system products.
The mechanism by which the yeast form of Blastomyces dermatitidis resists killing by human peripheral blood polymorphonuclear neutrophils (PMN) was investigated. The metabolic products of the oxidative burst generated during the interaction of PMN and B. dermatitidis or Candida albicans were detected by lucigenin- or luminol-enhanced chemiluminescence (CL). Interaction of PMN and C. albicans resulted in luminol-enhanced CL 100-fold greater than that generated by PMN and B. dermatitidis. This correlated with killing of C. albicans and resistance of B. dermatitidis. Since B. dermatitidis and PMN interactions resulted in significant lucigenin-enhanced CL, deficient luminol CL was not due to a lack of products from the NADPH oxidase system. Killed B. dermatitidis cells at 37 degrees C were more efficient than live cells in stimulating PMN for luminol-enhanced CL; however, only fragmented B. dermatitidis cells elicited luminol-enhanced CL equivalent to that of C. albicans. Since lysates of PMN were active in a cell-free hydrogen peroxide-peroxidase-halide system, resistance of B. dermatitidis to PMN was not due to a defect in PMN peroxidase. Taken together, these findings indicate that resistance of B. dermatitidis to killing by PMN results from inefficient generation of products from the peroxidase-dependent PMN microbicidal system.
Brummer
E
E
Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Kurita
N
N
Yoshida
S
S
Nishimura
K
K
Miyaji
M
M
D000166:Acridines; D001758:Blastomyces / Q000276:immunology* / Q000648:ultrastructure; D002176:Candida albicans / Q000276:immunology / Q000648:ultrastructure; D002478:Cells, Cultured; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism*; D010587:Phagocytosis; D016897:Respiratory Burst; D013696:Temperature
D000166:Acridines; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; D009195:Peroxidase