TY - JOUR
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.
N1 - Funding Information:
Potential conflicts of interest: D.P.K. has received research support and honoraria from Merck, Fujisawa, Enzon, Pfizer, and Schering-Plough. R.E.L. has received research support from Merck, Fujisawa, Pfizer, Enzon, and Schering-Plough. I.I.R. has received research support and honoraria from Schering-Plough, Astellas Pharma, Enzon, Merck, and Wyeth. A.S. is a member of the speakers’ bureaus of Merck, Cubist, and Pfizer. T.J.W. has cooperative research and development agreements with Vicuron (subsequently acquired by Pfizer) and Fujisawa (Astellas). All other authors: no conflicts.
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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U2 - 10.1086/589305
DO - 10.1086/589305
M3 - Article
C2 - 18500936
AN - SCOPUS:47649090076
SN - 0022-1899
VL - 198
SP - 186
EP - 192
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -