title: Caspofungin-mediated beta-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae.
abstract: BACKGROUND
  We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage.
  
  
  METHODS
  Using aniline blue staining, we compared patterns of beta-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-beta-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 microg/mL for R. oryzae; 0.0625 microg/mL for other isolates) increased exposure to beta-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-beta-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 beta-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins.
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Lamaris
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
authors.forename: Gregory S
authors.initials: GS
authors.lastname: May
authors.forename: Amar
authors.initials: A
authors.lastname: Safdar
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Issam I
authors.initials: II
authors.lastname: Raad
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D054714:Echinocandins / Q000494:pharmacology*; D005670:Fusarium / Q000187:drug effects; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000502:physiology*; D037181:Lectins, C-Type; D055666:Lipopeptides; D008565:Membrane Proteins / Q000235:genetics; D008271:Mycetoma / Q000188:drug therapy; D009419:Nerve Tissue Proteins / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012233:Rhizopus / Q000187:drug effects; D021681:Scedosporium / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics; D047071:beta-Glucans / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D000077336:Caspofungin; D054714:Echinocandins; D037181:Lectins, C-Type; D055666:Lipopeptides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; D000099181:Dectin-1