Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae

Gregory A. Lamaris, Russell E. Lewis, Georgios Chamilos, Gregory S. May, Amar Safdar, Thomas J. Walsh, Issam I. Raad, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticle

Abstract

Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of β-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-β-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH- tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin (32 μg/mL for R. oryzae; 0.0625 μg/mL for other isolates) increased exposure to β-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-β-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of β-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.

Original languageEnglish (US)
Pages (from-to)186-192
Number of pages7
JournalJournal of Infectious Diseases
Volume198
Issue number2
DOIs
StatePublished - Jul 15 2008
Externally publishedYes

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caspofungin
Glucans
Hyphae
Aspergillus
Neutrophils
Echinocandins
Aspergillus fumigatus
Scedosporium
Fusarium
anidulafungin
Fungi
Rhizopus
Anti-Idiotypic Antibodies
Monoclonal Antibodies

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae. / Lamaris, Gregory A.; Lewis, Russell E.; Chamilos, Georgios; May, Gregory S.; Safdar, Amar; Walsh, Thomas J.; Raad, Issam I.; Kontoyiannis, Dimitrios P.

In: Journal of Infectious Diseases, Vol. 198, No. 2, 15.07.2008, p. 186-192.

Research output: Contribution to journalArticle

Lamaris, Gregory A. ; Lewis, Russell E. ; Chamilos, Georgios ; May, Gregory S. ; Safdar, Amar ; Walsh, Thomas J. ; Raad, Issam I. ; Kontoyiannis, Dimitrios P. / Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae. In: Journal of Infectious Diseases. 2008 ; Vol. 198, No. 2. pp. 186-192.
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abstract = "Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of β-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-β-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH- tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin (32 μg/mL for R. oryzae; 0.0625 μg/mL for other isolates) increased exposure to β-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-β-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of β-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.",
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T1 - Caspofungin-mediated β-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae

AU - Lamaris, Gregory A.

AU - Lewis, Russell E.

AU - Chamilos, Georgios

AU - May, Gregory S.

AU - Safdar, Amar

AU - Walsh, Thomas J.

AU - Raad, Issam I.

AU - Kontoyiannis, Dimitrios P.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of β-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-β-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH- tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin (32 μg/mL for R. oryzae; 0.0625 μg/mL for other isolates) increased exposure to β-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-β-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of β-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.

AB - Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of β-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-β-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH- tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin (32 μg/mL for R. oryzae; 0.0625 μg/mL for other isolates) increased exposure to β-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-β-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of β-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.

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