Prevention of Infection

Reply from: ironjustice@aol . com

Date: 14 Jun 2007, 02:07

Prevention of Infection

I suppose this is .. **why** .. we are supposed to keep our
lactoferrin .. empty .. ?

The Journal of Immunology,
2007, 178: 6367-6373.
Copyright © 2007 by The American Association of Immunologists, Inc.

Human Polymorphonuclear Leukocytes Inhibit Aspergillus fumigatus
Conidial Growth by Lactoferrin-Mediated Iron Depletion1
Kol A. Zarember2,*, Janyce A. Sugui2,, Yun C. Chang, Kyung J. Kwon-
Chung3, and John I. Gallin3,*
* Laboratory of Host Defenses, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD
20892; and Laboratory of Clinical Infectious Diseases, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, MD 20892

Aspergillus fumigatus, a common mold, rarely infects humans, except
during prolonged neutropenia or in cases of chronic granulomatous
disease (CGD), a primary immunodeficiency caused by mutations in the
NADPH oxidase that normally produces fungicidal reactive oxygen
species. Filamentous hyphae of Aspergillus are killed by normal, but
not CGD polymorphonuclear leukocytes (PMN); however, the few studies
on PMN-mediated host defenses against infectious conidia (spores) of
this organism have yielded conflicting results, some showing that PMN
do not inhibit conidial growth, with others showing that they do, most
likely using reactive oxygen species. Given that CGD patients are
exposed daily to hundreds of viable A. fumigatus conidia, yet
considerable numbers of them survive years without infection, we
reasoned that PMN use ROS-independent mechanisms to combat
Aspergillus. We show that human PMN from both normal controls and CGD
patients are equipotent at arresting the growth of Aspergillus conidia
in vitro, indicating the presence of a reactive oxygen species-
independent factor(s). Cell-free supernatants of degranulated normal
and CGD neutrophils both suppressed fungal growth and were found to be
rich in lactoferrin, an abundant PMN secondary granule protein.
Purified iron-poor lactoferrin at concentrations occurring in PMN
supernatants (and reported in human mucosal secretions in vivo)
decreased fungal growth, whereas saturation of lactoferrin or PMN
supernatants with iron, or testing in the presence of excess iron in
the form of ferritin, completely abolished activity against conidia.
These results demonstrate that PMN lactoferrin sequestration of iron
is important for host defense against Aspergillus.

The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement in accordance with 18 U.S.C. Section 1734 solely to
indicate this fact.

1 This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Institute of Allergy and
Infectious Diseases, and the National Institutes of Health Clinical
Center.

2 K.A.Z. and J.A.S. contributed equally to this study.

3 Address correspondence and reprint requests to Dr. John I. Gallin,
10 Center Drive, RM 6-2551, MSC 1504, Bethesda, MD 20892-1504; E-mail
address: jgallin@cc.nih.gov or Dr. Kyung J. Kwon-Chung, 10 Center
Drive, RM 11C304, Bethesda, MD 20892; E-mail address: june kwon-
chung@nih.gov

4 Abbreviations used in this paper: CGD, chronic granulomatous
disease; CMFDA, carboxymethylfluoroscene diacetate; LF, lactoferrin;
PMN, polymorphonuclear leukocyte; XTT, 2,3-bis-(2-methoxy-4-nitro-5-
sulphenyl)-(2H)-tetrazolium-5-carboxanilide.

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This Website Copyright © 2007 by The American Association of
Immunologists, Inc. All rights reserved.

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<<snip>>
Lactoferrin probably exerts its effect at the level of viral
adsorption,
<<snip>>

: J Infect Dis 2002 Oct 15;186(8):1161-1164 Links

Lactoferrin Inhibits Enterovirus 71 Infection of Human Embryonal
Rhabdomyosarcoma Cells In Vitro.

Lin TY, Chu C, Chiu CH.

Department of Pediatrics, Chang Gung Children's Hospital, Kweishan,
Taoyuan,
Taiwan.

Enterovirus 71 (EV71), the newest member of Enterovirudae, is notable
for
its etiological role in epidemics of severe neurological diseases in
children. It appears to be emerging as an important virulent
neurotropic
enterovirus in the upcoming era of poliomyelitis eradication, whereas
no
effective vaccine or antiviral agents are available at this moment.
Human
and bovine lactoferrins, iron-binding proteins belonging to the
nonimmune
defense system, were assayed in vitro to assess their inhibiting
capacity on
the cytopathic effect of EV71 on human embryonal rhabdomyosarcoma
(RD)
cells. Both bovine and human lactoferrins were found to be potent
inhibitors
of EV71 infection (mean IC(50), 10.5-24.5 &mgr;g/mL and 103.3-185.0
&mgr;g/mL, respectively). Lactoferrin probably exerts its effect at
the

level of viral adsorption, since the ongoing infection could not be
further
inhibited after the EV71 penetrated RD cells.

PMID: 12355368 [PubMed - as supplied by publisher]

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