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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2011) 35, 335–343 (Printed in Great Britain)
Kojic acid, a secondary metabolite from Aspergillus sp., acts as an inducer of macrophage activation
Ana Paula D. Rodrigues*, Antônio Sergio C. Carvalho†, Alberdan S. Santos†, Claudio N. Alves†, José Luiz M. do Nascimento‡ and Edilene O. Silva*1
*Universidade Federal do Par, Instituto de Cincias Biolgicas, Laboratrio de Biologia Estrutural, Belm, Par, Brazil, †Universidade Federal do Par, Instituto de Cincias Exatas e Naturais, Laboratrio Desenvolvimento e Planejamento de Frmacos, Belm, Par, Brazil, and ‡Universidade Federal do Par, Instituto de Cincias Biolgicas, Laboratrio de Neuroqumica Molecular e Celular, Belm, Par, Brazil

KA (kojic acid) is a secondary metabolite isolated from Aspergillus fungi that has demonstrated skin whitening, antioxidant and antitumour properties among others. However, limited information is available regarding its effects on macrophages, the major cell involved in cell defence. The aim of the present study was to analyse whether KA affects functional properties related to macrophage activation, such as phagocytosis and spreading ability over a substrate. Treatment of resident macrophages with 50 μg/ml KA for 1 h induced both morphological and physiological alterations in cells. Immunofluorescence microscopy revealed enhanced cell spreading and an increase in cell surface exposure, associated with a rearrangement of microtubules, actin filaments and intermediate filaments. KA also potentiated phagocytosis by macrophages, as demonstrated by the increase in phagocytic activity towards yeast, when compared to untreated cells. KA increased the production of ROS (reactive oxygen species), but not NO (nitric oxide) production. Three tests were used to assess cell viability; MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], NR (neutral red) uptake and PI (propidium iodide) exclusion test, which showed that macrophages maintain their viability following KA treatment. Results indicate that KA can modulate macrophage activation through cytoskeleton rearrangement, increase cell surface exposure, enhance the phagocytic process and ROS production. The study demonstrates a new role for KA as a macrophage activator.

Key words: cytoskeleton, kojic acid, macrophage activation, phagocytosis, secondary metabolite

Abbreviations: DMEM, Dulbecco's modified Eagle's medium, FBS, fetal bovine serum, KA, kojic acid, LM, light microscopy, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, NBT, nitroblue tetrazolium salt, NO, nitric oxide, NR, neutral red, PBS–BSA–Tw, PBS, pH 8.0, containing 1.0% BSA and 0.01% Tween 20, PI, propidium iodide, ROS, reactive oxygen species, SEM, scanning electron microscopy, TEM, transmission electron microscopy

1To whom correspondence should be addressed (email

Received 2 February 2010/6 May 2010; accepted 2 November 2010

Published as Cell Biology International Immediate Publication 2 November 2010, doi:10.1042/CBI20100083

© The Author(s) Journal compilation © 2011 Portland Press Limited

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)