Ironjustic
Sun, Aug-21-05, 06:36
FEMS Immunology and Medical Microbiology Volume 45, Issue 2 ,
1 August 2005, Pages 103-112
doi:10.1016/j.femsim.2005.02.007 Copyright =A9 2005
Federation of European Microbiological Societies Published by
Elsevier B.V.
Iron and iron chelating agents modulate Mycobacterium
tuberculosis growth and monocyte-macrophage viability and
effector functions
Leandra Cronj=E9a, Nicole Edmondsona, b, Kathleen D. Eisenachb
and Liza Bornmana, ,
aDepartment of Biochemistry, University of Johannesburg, P.O.
Box 524, Auckland Park, Johannesburg 2006, South Africa
bDepartment of Pathology and Microbiology/Immunology,
University of Arkansas for Medical Sciences, Little Rock,
Arkansas, USA
Received 20 August 2004; revised 6 January 2005; accepted 18
February 2005. Available online 30 March 2005.
Abstract Excess of iron promotes Mycobacterium tuberculosis
infection, its replication and progression to clinical disease
and death from tuberculosis. Chelation of iron may reduce M.
tuberculosis replication, restore host defence mechanisms and
it could constitute an application in the prevention and
treatment strategies where both iron overload and tuberculosis
are prevalent. We investigated the effect of iron and iron
chelating agents, like desferrioxamine and silybin,
individually and in combination with iron on mycobacterial
number, viability in culture and after recovery from
monocyte-macrophages, together with monocyte-macrophages
viability and oxidative defence. Mycobacterial number and
viability in culture were assessed using real-time
quantitative PCR of H37Rv IS6110 DNA, 16S rRNA and 85B mRNA,
whereas the microplate AlamarBlueTM assay was used to detect
viability in culture post-infection. Mitochondrial membrane
potential and phosphatidyl serine exposure of
monocyte-macrophages, detected using Mitotracker Red
fluorescence and Annexin V binding, respectively, served as
indicators of host cell viability. Superoxide generation
served as marker of monocyte-macrophage effector functions.
Extracellular H37Rv showed a significant increase in number
and viability in presence of excess iron and, by large, a
significant decrease in number and viability in presence of
the iron chelating agents, silybin and desferrioxamine,
compared to cultivation without supplementation.
Intracellularly, excess iron increased H37Rv viability
significantly but reduced monocyte-macrophages mitochondrial
membrane potential and compromised superoxide production.
Desferrioxamine had little influence on intracellular
parameters, but consistently prevented effects of excess iron,
while silybin significantly altered most intracellular
parameters and mostly failed to prevent effects of excess
iron. These findings suggest that chelation therapy should be
considered in conditions of iron overload and that effective
chelating agents like desferrioxamine, with limited
intracellular access might need to be used in combination with
lypophilic chelating agents.
Keywords: Desferrioxamine; Silybin; H37Rv; Mycobacterium
tuberculosis; Iron chelation
Corresponding author. Tel.: + 27 11 489 2406; fax: + 27
11 489 2605
FEMS Immunology and Medical Microbiology Volume 45, Issue 2 ,
1 August 2005, Pages 103-112
Copyright =A9 2005 Elsevier B.V. All rights reserved.
ScienceDirect=AE is a registered trademark of Elsevier B.V.
Dietary Iron Associated With Pulmonary Tuberculosis In Rural
Africans A DGReview of :"Association of Pulmonary Tuberculosis
with Increased Dietary Iron" Journal of Infectious Diseases
10/17/2001 By James Adams
Increased dietary iron is associated with a 3.5 fold increase
in the estimated odds of developing active tuberculosis in
rural Africans.
Researchers from multiple institutions, including the
University of Zimbabwe School of Medicine in Harare, Zimbabwe,
and the National Institute of Child Health and Human
Development (NICHD) in Bethesda, Maryland, United States,
investigated the possibility that increased dietary iron is a
risk factor for tuberculosis.
"Exposure to high levels of dietary iron in the form of
traditional beer is associated with increased iron stores in
rural Africans," according to the investigators.
Ninety-eight pulmonary tuberculosis patients and 98 controls
from rural Zimbabwe were included in the study. Their dietary
iron history and human immunodeficiency virus (HIV) status
were evaluated.
Results showed that HIV seropositivity was associated with a
17.3-fold increase in the estimated odds of developing active
tuberculosis. Also, HIV seropositivity in patients treated for
tuberculosis was associated with a 3.8-fold increase in the
estimated hazard ratio of death.
Increased dietary iron was associated with a 3.5-fold increase
in the odds of developing active tuberculosis and a 1.3-fold
increase in the estimated hazard ratio of death.
The study was financially supported by the Office of Minority
Health to the Cell Biology and Metabolism Branch of the NICHD,
the Cell Biology and Metabolism Branch of the NICHD and the
J.F. Kapnek Charitable Trust in Harare, Zimbabwe. J Infect Dis
2001; 184: 936-939. "Association of Pulmonary Tuberculosis
with Increased Dietary Iron"
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man
Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
1 August 2005, Pages 103-112
doi:10.1016/j.femsim.2005.02.007 Copyright =A9 2005
Federation of European Microbiological Societies Published by
Elsevier B.V.
Iron and iron chelating agents modulate Mycobacterium
tuberculosis growth and monocyte-macrophage viability and
effector functions
Leandra Cronj=E9a, Nicole Edmondsona, b, Kathleen D. Eisenachb
and Liza Bornmana, ,
aDepartment of Biochemistry, University of Johannesburg, P.O.
Box 524, Auckland Park, Johannesburg 2006, South Africa
bDepartment of Pathology and Microbiology/Immunology,
University of Arkansas for Medical Sciences, Little Rock,
Arkansas, USA
Received 20 August 2004; revised 6 January 2005; accepted 18
February 2005. Available online 30 March 2005.
Abstract Excess of iron promotes Mycobacterium tuberculosis
infection, its replication and progression to clinical disease
and death from tuberculosis. Chelation of iron may reduce M.
tuberculosis replication, restore host defence mechanisms and
it could constitute an application in the prevention and
treatment strategies where both iron overload and tuberculosis
are prevalent. We investigated the effect of iron and iron
chelating agents, like desferrioxamine and silybin,
individually and in combination with iron on mycobacterial
number, viability in culture and after recovery from
monocyte-macrophages, together with monocyte-macrophages
viability and oxidative defence. Mycobacterial number and
viability in culture were assessed using real-time
quantitative PCR of H37Rv IS6110 DNA, 16S rRNA and 85B mRNA,
whereas the microplate AlamarBlueTM assay was used to detect
viability in culture post-infection. Mitochondrial membrane
potential and phosphatidyl serine exposure of
monocyte-macrophages, detected using Mitotracker Red
fluorescence and Annexin V binding, respectively, served as
indicators of host cell viability. Superoxide generation
served as marker of monocyte-macrophage effector functions.
Extracellular H37Rv showed a significant increase in number
and viability in presence of excess iron and, by large, a
significant decrease in number and viability in presence of
the iron chelating agents, silybin and desferrioxamine,
compared to cultivation without supplementation.
Intracellularly, excess iron increased H37Rv viability
significantly but reduced monocyte-macrophages mitochondrial
membrane potential and compromised superoxide production.
Desferrioxamine had little influence on intracellular
parameters, but consistently prevented effects of excess iron,
while silybin significantly altered most intracellular
parameters and mostly failed to prevent effects of excess
iron. These findings suggest that chelation therapy should be
considered in conditions of iron overload and that effective
chelating agents like desferrioxamine, with limited
intracellular access might need to be used in combination with
lypophilic chelating agents.
Keywords: Desferrioxamine; Silybin; H37Rv; Mycobacterium
tuberculosis; Iron chelation
Corresponding author. Tel.: + 27 11 489 2406; fax: + 27
11 489 2605
FEMS Immunology and Medical Microbiology Volume 45, Issue 2 ,
1 August 2005, Pages 103-112
Copyright =A9 2005 Elsevier B.V. All rights reserved.
ScienceDirect=AE is a registered trademark of Elsevier B.V.
Dietary Iron Associated With Pulmonary Tuberculosis In Rural
Africans A DGReview of :"Association of Pulmonary Tuberculosis
with Increased Dietary Iron" Journal of Infectious Diseases
10/17/2001 By James Adams
Increased dietary iron is associated with a 3.5 fold increase
in the estimated odds of developing active tuberculosis in
rural Africans.
Researchers from multiple institutions, including the
University of Zimbabwe School of Medicine in Harare, Zimbabwe,
and the National Institute of Child Health and Human
Development (NICHD) in Bethesda, Maryland, United States,
investigated the possibility that increased dietary iron is a
risk factor for tuberculosis.
"Exposure to high levels of dietary iron in the form of
traditional beer is associated with increased iron stores in
rural Africans," according to the investigators.
Ninety-eight pulmonary tuberculosis patients and 98 controls
from rural Zimbabwe were included in the study. Their dietary
iron history and human immunodeficiency virus (HIV) status
were evaluated.
Results showed that HIV seropositivity was associated with a
17.3-fold increase in the estimated odds of developing active
tuberculosis. Also, HIV seropositivity in patients treated for
tuberculosis was associated with a 3.8-fold increase in the
estimated hazard ratio of death.
Increased dietary iron was associated with a 3.5-fold increase
in the odds of developing active tuberculosis and a 1.3-fold
increase in the estimated hazard ratio of death.
The study was financially supported by the Office of Minority
Health to the Cell Biology and Metabolism Branch of the NICHD,
the Cell Biology and Metabolism Branch of the NICHD and the
J.F. Kapnek Charitable Trust in Harare, Zimbabwe. J Infect Dis
2001; 184: 936-939. "Association of Pulmonary Tuberculosis
with Increased Dietary Iron"
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man
Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking