Abstract
A persistent defect of Aspergillus killing was observed in the neutrophils of a 6-year-old patient with a systemic A. fumigatus infection which was highly refractory to anti-mycotic therapy. Aspergillus phagocytosis in vitro was normal, but nearly 80% of the ingested organisms (versus 30% in the controls) survived intracellularly during the 2-hr assay period. The patient's neutrophils showed a subnormal frequency of nitroblue tetrazolium reduction and a subnormal hexose monophosphate shunt activation in response to phagocytosis. The metabolic responsiveness, however, was clearly superior to that of chronic granulomatous disease neutrophils tested for comparison. The immune status of the patient and the following properties of his neutrophils were found to be normal: random and chemotactic motility, killing of S. aureus and C. albicans, and the contents of several granula enzymes. Our findings suggest the existence of neutrophil factors or functions which are required for killing Aspergillus, but not S. aureus and C. albicans.
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- Bretz U., Baggiolini M. Biochemical and morphological characterization of azurophil and specific granules of human neutrophilic polymorphonuclear leukocytes. J Cell Biol. 1974 Oct;63(1):251–269. doi: 10.1083/jcb.63.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bujak J. S., Kwon-Chung K. J., Chusid M. J. Osteomyelitis and pneumonia in a boy with chronic granulomatous disease of childhood caused by a mutant strain of Aspergillus nidulans. Am J Clin Pathol. 1974 Mar;61(3):361–367. doi: 10.1093/ajcp/61.3.361. [DOI] [PubMed] [Google Scholar]
- Cooper M. R., DeChatelet L. R., McCall C. E., LaVia M. F., Spurr C. L., Baehner R. L. Complete deficiency of leukocyte glucose-6-phosphate dehydrogenase with defective bactericidal activity. J Clin Invest. 1972 Apr;51(4):769–778. doi: 10.1172/JCI106871. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dewald B., Rindler-Ludwig R., Bretz U., Baggiolini M. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J Exp Med. 1975 Apr 1;141(4):709–723. doi: 10.1084/jem.141.4.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feigenson M. E., Baggiolini M. Capping of ricin-binding sites does not influence phagocytosis in human polymorphonuclear leukocytes. Acta Haematol. 1978;59(3):144–162. doi: 10.1159/000207757. [DOI] [PubMed] [Google Scholar]
- Halazun J. F., Anast C. S., Lukens J. N. Thyrotoxicosis associated with Aspergillus thyroiditis in chronic granulomatous disease. J Pediatr. 1972 Jan;80(1):106–108. doi: 10.1016/s0022-3476(72)80464-5. [DOI] [PubMed] [Google Scholar]
- Johnston R. B., Newman S. L. Chronic granulomatous disease. Pediatr Clin North Am. 1977 May;24(2):365–376. doi: 10.1016/s0031-3955(16)33424-1. [DOI] [PubMed] [Google Scholar]
- Keusch G. T., Douglas S. D., Mildvan D., Hirschman S. Z. 14 C-glucose oxidation in whole blood: a clinical assay for phagocyte dysfunction. Infect Immun. 1972 Mar;5(3):414–415. doi: 10.1128/iai.5.3.414-415.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keusch G. T., Douglas S. D., Ugurbil K. Intracellular bactericidal activity of leukocytes in whole blood for the diagnosis of chronic granulomatous disease of childhood. J Infect Dis. 1975 May;131(5):584–587. doi: 10.1093/infdis/131.5.584. [DOI] [PubMed] [Google Scholar]
- Kim M. H., Rodey G. E., Good R. A., Chilgren R. A., Quie P. G. Defective candidacidal capacity of polymorphonuclear leukocytes in chronic granulomatous disease of childhood. J Pediatr. 1969 Aug;75(2):300–303. doi: 10.1016/s0022-3476(69)80403-8. [DOI] [PubMed] [Google Scholar]
- Kosower N. S., Kosower E. M., Wertheim B., Correa W. S. Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide. Biochem Biophys Res Commun. 1969 Nov 6;37(4):593–596. doi: 10.1016/0006-291x(69)90850-x. [DOI] [PubMed] [Google Scholar]
- Lehrer R. I., Cline M. J. Interaction of Candida albicans with human leukocytes and serum. J Bacteriol. 1969 Jun;98(3):996–1004. doi: 10.1128/jb.98.3.996-1004.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I., Cline M. J. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J Clin Invest. 1969 Aug;48(8):1478–1488. doi: 10.1172/JCI106114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I. Functional aspects of a second mechanism of candidacidal activity by human neutrophils. J Clin Invest. 1972 Oct;51(10):2566–2572. doi: 10.1172/JCI107073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I., Jan R. G. Interaction of Aspergillus fumigatus Spores with Human Leukocytes and Serum. Infect Immun. 1970 Apr;1(4):345–350. doi: 10.1128/iai.1.4.345-350.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preisig E., Hitzig W. H. Nitroblue-tetrazolium test for the detection of chronic granulomatous disease--technical modification. Eur J Clin Invest. 1971 Sep;1(6):409–412. doi: 10.1111/j.1365-2362.1971.tb00550.x. [DOI] [PubMed] [Google Scholar]
- Raubitschek A. A., Levin A. S., Stites D. P., Shaw E. B., Fudenberg H. H. Normal granulocyte infusion therapy for aspergillosis in chronic granulomatous disease. Pediatrics. 1973 Feb;51(2):230–233. [PubMed] [Google Scholar]
- Sacchi F., Cisternino M. A., Clivio A., Ferrari F. A., Fortunato A., Nespoli L., Beretta A., Siccardi A. G. Disorders of candidacidal activity and other neutrophil functions in three cases of chronic candidiasis. Helv Paediatr Acta. 1979;34(6):607–616. [PubMed] [Google Scholar]
- Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]