Affiliation:
1. Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892.
Abstract
Neutrophils (PMNs) are a critical line of defense against Aspergillus fumigatus infection. Increased frequency of invasive aspergillosis has been observed in patients receiving corticosteroids, suggesting a deleterious effect of these compounds on PMN antifungal function. To investigate this hypothesis and to determine the potential preventive utility of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma), the effects of hydrocortisone (HCS) and dexamethasone (DXS) on PMN-induced damage of Aspergillus fumigatus hyphae were studied with or without pretreatment of PMNs with G-CSF and IFN-gamma. PMNs treated with HCS (> or = 3,000 microM) or DXS (> or = 10 microM) during a 2-h colorimetric tetrazolium metabolic assay (using methylthiotetrazolium) showed suppressed percentage of hyphal damage (P < 0.02). In addition, both HCS (> or = 30 microM) and DXS (> or = 1 microM) significantly suppressed oxidative burst measured as superoxide anion release by PMNs in response to opsonized and nonopsonized hyphae as well as to N-formylmethionyl leucyl phenylalanine. Pretreatment of PMNs with G-CSF (4,000 U/ml) and/or IFN-gamma (100 and 1,000 U/ml) for 90 min prevented the suppression of hyphal damage that occurred in the presence of HCS (3,000 microM; P < 0.01) or DXS (10 microM; P < or = 0.001). G-CSF (4,000 U/ml) and IFN-gamma (100 U/ml) combined had an additive effect on increasing the antifungal activity of HCS-treated but not of DXS-treated PMNs compared with IFN-gamma alone (P = 0.015). Thus, these findings reveal that corticosteroids impair PMN function in response to A. fumigatus and that G-CSF and IFN-gamma prevent this impairment.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference59 articles.
1. Evidence for the involvement of distinct signal transduction pathways in the regulation of constitutive and interferon gamma-dependent gene expression of NADPH oxidase components (gp 91-phox, p47-phox, and p22-phox) and high-affinity receptor for IgG (Fc gamma R-I) in human polymorphonuclear leukocytes;Amezaga M. A.;Blood,1992
2. Effect of dexamethasone on polypeptides synthesized in polymorphonuclear leukocytes;Blowers L. E.;FEBS Lett.,1985
3. Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis;Bonilla M. A.;N. Engl. J. Med.,1989
4. Bowen D. L. and A. S. Fauci. 1988. Adrenal corticosteroids p. 877-895. In J. I. Gallin I. M. Goldstein and R. Snyderman (ed.) Inflammation: basic principles and clinical correlates. Raven Press Ltd. New York.
5. Isolation of mononuclear cells and granulocytes from human blood: isolation of mononuclear cells by one centrifugation and of granulocytes by combining centrifugation and sedimentation at 1 g;Boyum A.;Scand. J. Clin. Lab. Invest. Suppl.,1968
Cited by
162 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献