HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print July 11, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0207090v1 82/4/839    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Orciuolo, E. Articles by Komanduri, K. V. Search for Related Content PubMed PubMed Citation Articles by Orciuolo, E. Articles by Komanduri, K. V.

(Journal of Leukocyte Biology. 2007;82:839-848.)
© 2007 by Society for Leukocyte Biology

Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis

Enrico Orciuolo^*,1, Marta Stanzani, Martina Canestraro^*, Sara Galimberti^*, Giovanni Carulli^*, Russell Lewis, Mario Petrini^* and Krishna V. Komanduri

^* Hematology Section, Department of Oncology, Transplant and Advances in Medicine, University of Pisa, Italy;
Institute of Hematology and Clinical Oncology ‘L. e A. Seràgnoli’, University of Bologna, Italy; and
Department of Infectious Diseases Infection Control and Employee Health and
Transplant Immunology Section, Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, Texas, USA

¹ Correspondence: Department of Oncology, Transplant and Advances in Medicine, Hematology Section, University of Pisa, Ospedale S. Chiara, Via Roma 56, 56100 Pisa, Italy. E-mail: orci{at}sssup.it

ABSTRACT

Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. In stem cell transplant recipients, IA now occurs most frequently in the setting of therapy with corticosteroids, including methylprednisolone (MP). We showed previously that gliotoxin (GT), an AF-derived mycotoxin, induces apoptosis in monocytes and dendritic cells, resulting in the suppression of AF-specific T cell responses. We examined the ability of GT to induce apoptosis in polymorphonuclear leukocytes (PMN) and assessed GT effects on important neutrophil functions, including phagocytic function, degranulation, myeloperoxidase activity, and the production of reactive oxygen species (ROS). In contrast to its effects on monocytes, PMN remained resistant to GT-mediated apoptosis. Although many essential neutrophil functions were unaffected, GT inhibited phagocytosis and also induced a decrease in ROS generation by PMN. In contrast, MP therapy potentiated ROS production, suggesting a mechanism that may facilitate tissue injury in IA. Distinct from its effects on untreated PMN, GT augmented ROS production in MP-treated PMN. Our results suggest that although GT may suppress the adaptive immune response, GT may also serve to increase PMN-mediated inflammation, which is likely to play an important role in tissue destruction in the setting of IA.

Key Words: polymorphonuclear leukocytes • micotoxin • immune response